Nitrogen-containing bicyclic compounds and drugs containing the same as the active ingredient

ABSTRACT

A nitrogen-containing bicyclic compound of formula (I) or a pharmaceutically acceptable salt thereof (wherein the symbols have the same meanings as described in the specification). 
     
       
         
         
             
             
         
       
     
     The compound of formula (I) has an inhibitory activity against PDE7 and it is useful for the prevention and/or treatment of various diseases, i.e. autoimmune diseases (ulcerative colitis, Crohn&#39;s disease, rheumatism, psoriasis, multiple sclerosis, collagenosis, etc.), inflammatory diseases (obstructive pulmonary disease, sepsis, pancreatitis, sarcoidosis, nephritis, hepatitis, enteritis, etc.), allergic diseases (asthma, allergic rhinitis, allergic conjunctivitis, seasonal conjunctivitis, atopic dermatitis, etc.), rejection of organ transplants, serious graft versus host disease (GVHD), diabetic disease, osteoporosis, bone fracture, restenosis, atherosclerosis, obesity, ischemic reperfusion injury, depression, Parkinson&#39;s disease, dementia, leukemia, etc.

TECHNICAL FIELD

The present invention relates to a nitrogen-containing bicyclic compoundor a pharmacologically acceptable salt thereof and a pharmaceuticalcomposition comprising it as active ingredient.

More specifically, the present invention relates to

-   (1) a compound of formula (I)

or a pharmacologically acceptable salt thereof,

-   (2) a method for the preparation thereof, and-   (3) a pharmaceutical composition comprising it as active ingredient.

BACKGROUND ART

Cyclic nucleotides such as cyclic adenosine-3′,5′-monophosphate (c-AMP)and cyclic guanosine 3′,5′-monophosphate (c-GMP) are concerned withintracellular signal transduction molecules as second messengers. Thesecyclic nucleotides are degraded by a group of hydrolases generallycalled phosphodiesterase PDE isozyme) into inactive 5′-AMP and 5′-GMP,respectively.

Up to date, the presence of 11 families of PDE1 to PDE11 has beenconfirmed (see Current Opinion in Cell Biology, 12, 174-179 (2000)). PDEisozymes have differences in specificity and affinity to substrates,i.e. c-AMP and c-GMP, cell distribution and tissue distribution, etc.,and each isozyme has different function in vivo.

Among these PDEs, PDE7 is a phosphodiesterase which has specificaffinity to cAMP, and it is reported that it is not inhibited byrolipram, which is a PDE4 inhibitor specific to PDE4 (see J. Biol.Chem., 268, 12925 (1993)). PDE7 is important in activation of T-cellsand it is implied that it is useful for the prevention and treatment ofT cell-dependent diseases (see Science, 283, 848 (1999)). Also, PDE7 isexpressed in airway epitheliocytes, and so it is also implied that it isprobable that PDE7 is effective for the diseases in airway (see Am. JRespir. Cell Mol. Biol., 20, 292 (1999)).

Therefore, a drug which inhibits PDE7 is thought to be useful for theprevention and/or treatment of various diseases, i.e. autoimmunediseases (ulcerative colitis, Crohn's diesaes, rheumatism, psoriasis,multiple sclerosis, collagenosis, etc.), inflammatory diseases(obstructive pulmonary diseases, sepsis, pancreatitis, sarcoidosis,nephritis, hepatitis, enteritis, etc.), allergic diseases (asthma,allergic rhinitis, allergic conjunctivitis, seasonal conjunctivitis,atopic dermatitis, etc.), rejection of an organ transplant, graft versushost diseases (GVHD), diabetic diseases, osteoporosis, bone fracture,restenosis, arteriosclerosis, obesity, ischemic reperfusion injury,depression, Parkinson's diseases, dementia, leukemia, etc.

Isoquinoline derivatives are known as follows: for example, inJP63-280069(A), it is disclosed that a compound of formula (A)

(wherein A^(A) is benzo or thieno and R^(2A) and R^(3A) areindependently hydrogen or (C1-5)alkyl, or taken together with the carbonatom to which they are attached to form 5 or 6 membered carbocycle andR^(11A) is (C1-4)alkyl, halogen, hydroxy and mA is 0, 1, 2 or 3 whenA^(A) is benzo, D^(A) is Ib^(A), etc.:

R^(1A) is hydrogen, (C1-10)alkyl etc, R^(5′A) is hydrogen or(C1-4)alkyl, R^(4A) is (C1-4)alkoxy or —NR^(9A)R^(10A) (wherein R^(9A)and R^(10A) are independently hydrogen, C1-12 branched or unbranchedalkyl, alkenyl or alkynyl, etc., or R^(9A) and R^(10A) are takentogether with the carbon atom to which they are attached to formpyrrolidinyl, piperidinyl, morpholinyl or piperazinyl, etc.)) hasheart-protecting activity (groups are extracted for description).

Khim. Geterotsikl. Soedin., 946-949, 7, (1994) discloses a compound of2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ylidene)-1-phenylmethan-1-one(Reg No. 163769-77-5).

The specification of WO 02/010135 discloses that a compound of formula(B)

(wherein the explanation of groups are as described in the specificationof WO02/010135.) has a cannabinoid (CB) 2 receptor agonizing activity,but no description is found on PDE7 inhibitory activity therein.

DISCLOSURE OF THE INVENTION

In order to find a compound having a PDE7 inhibitory activity, thepresent inventors have conducted intensive studies and found, as aresult, that the objects can be accomplished by nitrogen-containingbicyclic compounds of formula (I) and pharmaceutically acceptable saltsthereof, and thus the present invention has been accomplished.

Also, the present inventors have found that some compounds among thecompound of formula (I) has cannabinoid (CB)2 receptor agonizingactivity, and thus the present invention was accomplished.

Cannabinoid is a generic name of Δ9-tetrahydrocannabinol (abbreviated asΔ9-THC hereafter) which is a main ingredient of marijuana, which is madefrom hemp, and its analogues (Deway, Pharmacol. Rev., 38, 15-178(1996)). It is known as a substance which causes euphoria, sleepiness,hallucination, relief from mental tense, etc (Hollister, Pharmacol.Rev., 38, 1-20 (1986)).

Aside from the previous central effects, it is reported that thereactivity of lymphocytes is decreased in habitual users of marijuana(Naha et al., Science, 183, 419-420 (1974)), that marijuana or Δ9-THClowers the ability of leucocytoplania and the function of macrophages,etc. in vitro (Schwartzfarb et al., J. Clin. Pharmacol., 14, 35-41(1974); Lopez-Capero et al., J Leuk. Biol., 39, 679-686 (1986)), andthat it lowers the resistance to virus infection (Morahan et al.,Infect. Immun., 23, 670-674 (1979)), etc. These facts implies thatcannabinoid acts not only on central nervous system but also onperiphery (particularly immune system).

First reported cannabinoid receptor is CB1 receptor, which was clonedfrom rat cerebral cortex cDNA library in 1990 (Matsuda et al., Nature.,346, 561-564 (1990)). Afterwards, CB2 receptor was cloned from humanpromyelogenic leukemia cell line HL-60cDNA library (Murano et al.,Nature., 365, 61-65 (1993)). It was revealed that CB1 is mainlyexpressed in brains and CB2 in those cells which are responsible forimmunity, e.g. spleens.

It had been conceived to adapt cannabinoid to medical care for a longtime (Mechiulan, CRC Press, Boca Raton., 1-20 (1986); Razdan et al., MedRes. Rev., 3, 119-146 (1983)), and some of them are used aspharmaceuticals already such as Cesamet (Ward and Holmes, Drugs., 30,127-144 (1985)). These are conceived to take effect via CB1.

On the other hand, the physiological roles of CB2 receptor, which is aperipheral receptor, is not revealed enough yet, but it is implied thata compound which acts on CB2 receptor (agonist, antagonist) modulatesinflammation and immune. Moreover, it is expected that it is effectivefor a pain accompanying inflammation (Calignano et al., Nature., 394,277-281 (1998)).

From these above, a pharmaceutical agent which acts on CB2 receptorspecifically, is useful for the prevention and/or treatment of variousdiseases, that is, asthma, nasal allergy, atopic dermatology, autoimmunediseases (multiple sclerosis, colitis, etc.), rheumatism, arthritis,immune dysfunction (acquired immunodeficiency syndrome etc.), pains(postoperative pain, carcinomatous pain, etc.

That is, the present invention relates to

-   (1) a compound of formula (I)

wherein R¹ and R² are each independently, (1) hydrogen atom, or (2) C1-8alkyl, or

R¹ and R² may be taken together with the carbon atom to which they areattached to form Cyc1,

wherein R¹ and R² do not represent hydrogen atom at the same time;

Z is (1) —CR³R⁴—, (2) —O—, (3) —S—, or (4) a bond;

R³ and R⁴ are each independently, (1) hydrogen atom, (2) C1-8 alkyl, (3)C1-8 alkoxy, or (4) hydroxy, or

R³ and R⁴ may be taken together with the carbon atom to which they areattached to form Cyc1 or —C(O)—;

R⁵ and R⁶ are each independently, (1) hydrogen atom, or (2) C1-8 alkyl,or

R⁵ and R⁶ may be taken together with the carbon atom to which they areattached to form Cyc1;

Cyc1, which is represented by R¹ and R², R³ and R⁴, R⁵ and R⁶ is, eachindependently, (1) C3-10 cycloalkyl, or (2) 3-10 membered monocyclicheteroring comprising 1-2 of heteroatom selected from oxygen, nitrogenand sulfur, and Cyc1 may be substituted with R¹⁰;

R¹⁰ is (1) C1-8 alkyl, (2) C1-8 alkoxy, (3) hydroxy, (4) —COOR¹¹, (5)oxo, (6) —SO₂R¹², or (7) —COR¹³;

R¹¹ is hydrogen atom, or C1-8 alkyl;

R¹² and R¹³ are (1) C1-8 alkyl, or (2) phenyl which may be substitutedwith C1-8 alkyl;

R⁷ and R⁸ are each independently, (1) hydrogen atom, (2) C1-8 alkyl, (3)C1-8 alkoxy, (4) hydroxy, (5) cyano, (6) halogen atom, (7) —COOR¹⁴, (8)—CONR¹⁵R¹⁶, (9) Cyc2, (10) C2-8 alkenyl, (11) C2-8 alkynyl, (12)—NR⁵¹R⁵², (13) nitro, (14) formyl, (15) C2-8 acyl, (16) C1-8 alkylsubstituted with hydroxy, C1-8 alkoxy, Cyc2, —NR⁵¹R⁵², or —NR⁵³-Cyc2,(17) —NR⁵⁴COR⁵⁵, (18) —NR⁵⁶SO₂R⁵⁷, (19) —SO₂NR⁵⁸R⁵⁹, (20) C2-8 alkenylsubstituted with —COOR¹⁴, (21) —CH═N—OH, (22) —(C1-8alkylene)-NR⁶⁰—(C1-8 alkylene)-R⁶¹, (23) C1-8 alkylthio, (24) C1-8 alkylsubstituted with 1-3 of halogen atom, (25) C1-8 alkoxy substituted with1-3 of halogen atom, (26) C1-8 alkoxy substituted with Cyc2, (27)—O-Cyc2, (28) —OSO₂R⁶⁵, or (29) —CH═N—OR¹³⁷;

R¹⁴ is hydrogen atom, or C1-8 alkyl;

R¹⁵ and R¹⁶ are each independently hydrogen atom or C1-8 alkyl;

R⁵¹ and R⁵², R⁵⁸ and R⁵⁹ are each independently, hydrogen atom, or C1-8alkyl;

R⁵³, R⁵⁴, R⁵⁶ and R⁶⁰ are each independently, hydrogen atom, or C1-8alkyl;

R⁵⁵ is hydrogen atom, C1-8 alkyl, or C1-8 alkoxy;

R⁵⁷ is C1-8 alkyl;

R⁶¹ is —NR⁶²R⁶³ or hydroxy;

R⁶² and R⁶³ are each independently, hydrogen atom, or C1-8 alkyl;

R⁶⁵ is C1-8 alkyl;

R¹³⁷ is C1-8 alkyl;

(hereinafter it is abbreviated as ring;) is Cyc2 wherein the group whichattaches to carbonyl is carbon;

R⁷, R⁸ and Cyc2 represented by ring are each independently, (1) C3-15mono-, bi- or tri-cyclic (fused or spiro)carboring, or (2) 3-15 memberedmono-, bi- or tri-cyclic (fused or spiro)heteroring comprising 1-4 ofheteroatom selected from oxygen, nitrogen and sulfur;

Cyc2 may be substituted with 1-5 of R¹⁷ or R¹⁷′;

R¹⁷ is (1) C1-8 alkyl, (2) C2-8 alkenyl, (3) C2-8 alkynyl, (4) C1-8alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7) halogen atom, (8) nitro,(9) oxo, (10)carboxy, (11) formyl, (12) cyano, (13) —NR¹⁸R¹⁹, (14)phenyl, phenoxy or phenylthio, which may be substituted with 1-5 of R²⁰,(15) C1-8 alkyl, C2-8 alkenyl, C1-8 alkoxy or C1-8 alkylthio, which maybe substituted with 1-5 of R²¹ (16) —OCOR²², (17) —CONR²³R²⁴, (18)—SO₂NR²⁵R²⁶, (19) —COOR²⁷, (20) —COCOOR²⁸, (21) —COR²⁹, (22) —COCOR³⁰,(23) —NR³¹COR³², (24) —SO₂R³³, (25) —NR³⁴SO₂R³⁵, or (26) —SOR⁶⁴;

R¹⁸ and R¹⁹, R³¹ and R³⁴ are each independently, hydrogen atom, or C1-8alkyl;

R²⁰ and R²¹ are C1-8 alkyl, C1-8 alkoxy, hydroxy, halogen atom, nitro,or —COOR³⁶;

R²² and R⁶⁴ are each independently C1-8 alkyl;

R²³, R²⁴, R²⁵ and R²⁶ are each independently hydrogen atom, C1-8 alkyl,or phenyl;

R²⁷, R²⁸, R²⁹, R³⁰, R³², R³³ and R³⁵ are (1) C1-8 alkyl, (2) C2-8alkenyl, (3) C1-8 alkyl substituted with 1-5 of R³⁷, (4) diphenylmethyl,(5) triphenylmethyl, (6) Cyc3, (7) C1-8 alkyl or C2-8 alkenylsubstituted with Cyc3, (8) C1-8 alkyl substituted with —O-Cyc3, —S-Cyc3or —SO₂-Cyc3;

R³⁶ is hydrogen atom, or C1-8 alkyl;

R³⁷ is C1-8 alkoxy, C1-8 alkylthio, benzyloxy, halogen atom, nitro or—COOR³⁸;

R³⁸ is hydrogen atom, C1-8 alkyl or C2-8 alkenyl;

Cyc3 is (1) C3-15 mono-, bi- or tri-cyclic (fused or spiro)carboring, or(2) 3-15 membered mono-, bi- or tri-cyclic (fused- or spiro)heteroringcomprising 1-4 of heteroatom selected from oxygen, nitrogen and sulfur;

Cyc3 may be substituted with 1-5 of R³⁹;

R³⁹ is (1) C1-8 alkyl, (2) C2-8 alkenyl, (3) C2-8 alkynyl, (4) C1-8alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7) halogen atom, (8) nitro,(9) oxo, (10) cyano, (11) benzyl, (12) benzyloxy, (13) C1-8 alkyl, C1-8alkoxy or C1-8 alkylthio substituted with 1-5 of R⁴⁰, (14) phenyl,phenoxy, phenylthio, phenylsulfonyl or benzoyl which may be substitutedwith 1-5 of R⁴¹, (15) —OCOR⁴², (16) —SO₂R⁴³, (17) —NR⁴⁴COR⁴⁵, (18)—SO₂NR⁴⁶R⁴⁷, (19) —COOR⁴⁸, or (20) —NR⁴⁹R⁵⁰;

R⁴⁰ is halogen atom;

R⁴¹ is C1-8 alkyl, C1-8 alkoxy, halogen atom, or nitro;

R⁴², R⁴³ and R⁴⁵ are C1-8 alkyl;

R⁴⁴ and R⁴⁸ are hydrogen atom or C1-8 alkyl;

R⁴⁶ and R⁴⁷, R⁴⁹ and R⁵⁰ are each independently, hydrogen atom or C1-8alkyl;

R^(17′) is (1) SH, (2) —NR⁶⁶CHO, (3) Cyc5, (4) C1-8 alkyl, C2-8 alkenylor C2-8 alkynyl substituted with Cyc5, (5) —CO—(NH-amino acidresidue-CO)_(n)—OH, (6) —NR⁶⁷CONR⁶⁸R⁶⁹, (7) —CONR⁷⁰NR⁷¹R⁷², (8)—CONR⁷³R⁷⁴, (9) —CONR⁷⁵COR⁷⁶, (10) —C(S)NR⁷⁷R⁷⁸, (11) —CONR⁷⁹C(S)COOR⁸⁰,(12) —NR⁸¹COCOOR⁸², (13) —NR⁸³COOR⁸⁴, (14) —CONR⁸⁵C(S)R⁸⁶, (15) —OCOR⁸⁷,(16) —SOR⁸⁸, (17) —CONR⁸⁹R⁹⁰, (18) —SO₂NR⁹¹R⁹², (19) —COOR⁹³, (20)—COCOOR⁹⁴, (21) —COR⁹⁵, (22) —COCOR⁹⁶, (23) —NR⁹⁷COR⁹⁸, (24) —SO₂R⁹⁹,(25) —NR¹⁰⁰SO₂R¹⁰¹, or (26) —NR¹⁰²R¹⁰³;

n is an integer of 1 or 2;

R⁶⁶, R⁷³, R⁷⁵, R⁷⁷, R⁷⁹, R⁸¹, R⁸³, R⁸⁵, R⁹⁷, R¹⁰⁰ and R¹⁰² are hydrogenatom, or C1-8 alkyl;

R⁶⁷ and R⁶⁸, R⁷⁰ and R⁷¹ are each independently, hydrogen atom, or C1-8alkyl;

R⁸⁹ and R⁹¹ are (1) hydrogen atom, (2) C1-8 alkyl, (3) phenyl, or (4)C1-8 alkyl substituted with cyano or C1-8 alkoxy;

R¹⁰³ is Cyc6;

R⁶⁹, R⁷², R⁷⁴, R⁷⁶, R⁷⁸, R⁸⁰, R⁸², R⁸⁴, R⁸⁶, R⁸⁷, R⁸⁸, R⁹⁰ and R⁹² are(1) hydrogen atom, (2) C1-8 alkyl, (3) C2-8 alkenyl, (4) C2-8 alkynyl,(5) C1-8 alkyl substituted with 1-5 of R¹⁰⁴, (6) diphenylmethyl, (7)triphenylmethyl, (8) Cyc6, (9) C1-8 alkyl or C2-8 alkenyl substitutedwith Cyc6, or (10) C1-8 alkyl substituted with —O-Cyc6, —S-Cyc6 or—SO₂-Cyc6;

R¹⁰⁴ is (1) C1-8 alkoxy, (2) C1-8 alkylthio, (3)benzyloxy, (4) halogenatom, (5) nitro, (6) —COOR¹⁰⁵, (7) cyano, (8) —NR¹⁰⁶R¹⁰⁷, (9)—NR¹⁰⁸COR¹⁰⁹, (10) hydroxy, (11) SH, (12) —SO₃H, (13) —S(O)OH, (14)—OSO₃H, (15) C2-8 alkenyloxy, (16) C2-8 alkynyloxy, (17) —COR¹¹⁰, (18)—SO₂R¹¹¹, or (19) C1-8 alkoxy or C1-8 alkylthio substituted withhydroxy;

R¹⁰⁵ is hydrogen atom, C1-8 alkyl, or C2-8 alkenyl;

R¹⁰⁶ and R¹⁰⁷ are each independently, hydrogen atom, or C1-8 alkyl;

R¹⁰⁸ is hydrogen atom, or C1-8 alkyl;

R¹⁰⁹ and R¹¹¹ are C1-8 alkyl;

R¹¹⁰ is C1-8 alkyl, or halogen atom;

wherein R⁸², R⁸⁴ and R⁸⁶ are not hydrogen atom;

wherein R⁸⁷ and R⁸⁸ are not hydrogen atom and C1-8 alkyl;

wherein R⁹⁰ and R⁹² are not hydrogen atom, C1-8 alkyl or phenyl;

R⁹³, R⁹⁴, R⁹⁵, R⁹⁶, R⁹⁸, R⁹⁹ and R¹⁰¹ are (1) C2-8 alkynyl, (2) C1-8alkyl substituted with R¹²⁸ which may be substituted with 1-4 of R¹²⁹,(3) Cyc8, (4) C1-8 alkyl or C2-8 alkenyl substituted with Cyc8, or (5)C1-8 alkyl substituted with —O-Cyc8, —S-Cyc8 or —SO₂-Cyc8;

R¹²⁸ is (1) cyano, (2) —NR¹⁰⁶R¹⁰⁷, (3) —NR¹⁰⁸COR¹⁰⁹, (4) hydroxy, (5)SH, (6) —SO₃H, (7) —S(O)OH, (8) —OSO₃H, (9) C2-8 alkenyloxy, (10) C2-8alkynyloxy, (11) —COR¹¹⁰, (12) —SO₂R¹¹¹, or (13) C1-8 alkoxy or C1-8alkylthio substituted with hydroxy;

R¹²⁹ has the same meaning as R¹⁰⁴;

Cyc5 and Cyc6 may be substituted with 1-5 of R¹¹²;

R¹¹² is (1) C1-8 alkyl, (2) C2-8 alkenyl, (3) C2-8 alkynyl, (4) C1-8alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7) halogen atom, (8) nitro,(9) oxo, (10) cyano, (11) benzyl, (12)benzyloxy, (13) C1-8 alkyl, C1-8alkoxy or C1-8 alkylthio substituted with 1-5 of R¹¹³, (14) phenyl,phenoxy, phenylthio or benzoyl, which may be substituted with 1-5 ofR¹¹⁴, (15) —COR¹¹⁵, (16) —SO₂R¹¹⁶, (17) —NR¹¹⁷COR¹¹⁸, (18)—SO₂NR¹¹⁹R¹²⁰, (19) —COOR¹²¹ (20) —NR¹²²R¹²³, (21) —COR¹²⁴, (22)—CONR¹²⁵R¹²⁶, (23) SH, (24) C1-8 alkyl substituted with hydroxy or—NR¹²⁷-benzoyl, or (25) Cyc7;

R¹¹³ is halogen atom;

R¹¹⁴ is C1-8 alkyl, C1-8 alkoxy, halogen atom, or nitro;

R¹¹⁵, R¹¹⁶ and R¹¹⁸ are C1-8 alkyl;

R¹¹⁷, R¹²¹, R¹²⁴ and R¹²⁷ are hydrogen atom, or C1-8 alkyl;

R¹¹⁹ and R¹²⁰, R¹²² and R¹²³, R¹²⁵ and R¹²⁶ are each independently,hydrogen atom or C1-8 alkyl;

Cyc7 may be substituted with 1-5 group selected from (1) C1-8 alkyl, (2)C1-8 alkoxy, (3) halogen atom, or (4) nitro;

Cyc8 may be substituted with R¹³⁰, and it further may be substitutedwith 1-4 of R¹³¹;

R¹³⁰ is (1) —COR¹²⁴, (2) —CONR¹²⁵R¹²⁶, (3) SH, (4) C1-8 alkylsubstituted with hydroxy or —NR¹²⁷-benzoyl, or (5) Cyc7;

R¹³¹ has the same meaning as R¹¹²;

Cyc5, Cyc6, Cyc7 and Cyc8 are (1) C3-15 mono-, bi- or tri-cyclic (fusedor spiro)carboring, or (2) 3-15 membered mono-, bi- or tri-cyclic (fusedor spiro)heteroring comprising 1-4 of heteroatom selected from 1-4 ofoxygen, nitrogen or sulfur;

wherein when R^(17′) is Cyc5, Cyc5 is not phenyl which may besubstituted with 1-5 selected from C1-8 alkyl, C1-8 alkoxy, hydroxy,halogen atom, nitro, —COOH, or —COO—(C1-8 alkyl);

wherein Cyc7 is not phenyl;

Cyc4 is (1) C5-7 monocyclic carboring, or (2) 5-7 membered monocyclicheteroring comprising 1-2 of heteroatom selected from oxygen, nitrogenand sulfur;

(abbreviated as dashed line a hereafter;) and

(abbreviated as dashed line b hereafter;) are (1) a bond, or (2) adouble bond;

R⁹ (1) does not exist or (2) is hydrogen atom;

wherein

-   1) when dashed line a is a bond, dashed line b is a double bond, and    R⁹ does not exist,-   2) when dashed line a is a double bond, dashed line b is a bond, and    R⁹ is hydrogen atom and R⁶ does not exist, and-   3)    2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one    is excluded, or a pharmacologically acceptable salt thereof,-   (2) the compound according to above (1), wherein Z in formula (I) is    —S— or a bond, or a pharmacologically acceptable salt thereof,-   (3) the compound according to above (1), in formula (I), wherein

(i) Z is —CR³R⁴—, or —O—, and at least either of R⁷ or R⁸ is (24) C1-8alkyl substituted with 1-3 of halogen atom, (25) C1-8 alkoxy substitutedwith 1-3 of halogen atom, (26) C1-8 alkoxy substituted with Cyc2, (27)—O-Cyc2, (28) —OSO₂R⁶⁵, or (29) —CH═N—OR¹³⁷, or

(ii) Z is —CR³R⁴—, or —O—, and at least one Cyc2 which is represented byR⁷, R⁸ or ring is substituted with at least one R^(17′) or apharmacologically acceptable salt thereof,

-   (4) the compound according to above (1), which is represented by    formula (I′)

wherein, R^(1′) and R^(2′) are each independently, C1-8 alkyl, Z′ is—CR^(3′)R^(4′)—, or —O—, R^(3′) and R^(4′) are each independently,hydrogen atom, C1-8 alkyl, or hydroxy,

R^(7′) and R^(8′) are each independently, hydrogen atom, C1-8 alkyl,C1-8 alkoxy, hydroxy, cyano, halogen atom, —COOR¹⁴, —CONR¹⁵R¹⁶, Cyc2,—NR⁵¹R⁵², formyl, hydroxy or C1-8 alkyl substituted with C1-8 alkoxy, or—SO₂NR⁵⁸R⁵⁹;

Cyc2 represented by

may be substituted with 1-5 of R^(17″);

R^(17″) is C1-8 alkyl, C1-8 alkoxy, hydroxy, halogen atom, nitro, oxo,(10) carboxy, (11) formyl, (12) cyano, (13) —NR¹⁸R¹⁹, (15) C1-8 alkylsubstituted with 1-5 of R²¹, (17) —CONR²³R²⁴, (19) —COOR²⁷, (21) —COR²⁹,(23) —NR³¹COR³², or (25) —NR³⁴SO₂R³⁵ and the other symbols have the samemeaning as above (1);) or a pharmacologically acceptable salt thereof,

-   (5) a PDE7 inhibitor comprising the compound according to above (1),    or a pharmacologically acceptable salt as active ingredient,-   (6) a pharmaceutical composition for the prevention and/or treatment    of autoimmune diseases, inflammatory diseases, allergic diseases,    rejection of an organ transplant, graft versus host disease (GVHD),    diabetic diseases, osteoporosis, bone fracture, re-stenosis,    arteriosclerosis, obesity, ischemic reperfusion injury, depression,    Parkinson's diseases, dementia or leukemia, comprising the compound    according to above (1) or a pharmacologically acceptable salt    thereof as active ingredient, and-   (7) a pharmaceutical composition for the prevention and/or treatment    of asthma, allergy rhinitis, atopic dermatitis, autoimmune diseases,    rheumatism, postoperative pain and/or carcinomatous pain, comprising    the compound described in above (2) or (3) or a pharmacologically    acceptable salt as active ingredient.

In the present specification, C1-8 alkyl is methyl, ethyl, propyl,butyl, pentyl, hexyl, heptyl, octyl and isomers thereof.

In the present specification, C2-8 alkenyl is ethenyl, propenyl,butenyl, pentenyl, hexenyl, heptenyl, octenyl and isomers thereof.

In the present specification, C2-8 alkynyl is ethynyl, propynyl,butynyl, pentynyl, hexynyl, heptynyl, octynyl and isomers thereof.

In the present specification, C1-8 alkoxy is methoxy, ethoxy, propoxy,butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy and isomers thereof.

In the present specification, C2-8 alkenyloxy is ethenyloxy,propenyloxy, butenyloxy, pentenyloxy, hexenyloxy, heptenyloxy,octenyloxy and isomers thereof.

In the present specification, C2-8 alkynyloxy is ethynyloxy,propynyloxy, butynyloxy, pentynyloxy, hexynyloxy, heptynyloxy,octynyloxy and isomers thereof.

In the present specification, C1-8 alkylthio is methylthio, ethylthio,propylthio, butylthio, pentylthio, hexylthio, heptylthio, octylthio andisomers thereof.

In the present specification, halogen atom is chlorine, bromine,fluorine, iodine.

In the present specification, C3-10 cycloalkyl is cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclononyl, cyclodecyl.

In the present specification, C2-8 acyl is, acetyl, propanoyl, butanoyl,pentanoyl, hexanoyl, heptanoyl, octanoyl and isomers thereof.

In the present specification, C1-8 alkylene is methylene, ethylene,trimethylene, tetramethylene, pentamethylene, hexamethylene,heptamethylene, octamethylene and isomers thereof.

In the present specification, C5-7 monocyclic carboring is, for example,cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene,cycloheptene, cyclopentadiene, cyclohexadiene, cycloheptadiene, benzene,etc.

In the present specification, 5-7 membered monocyclic heteroringcomprising 1-2 of heteroatom selected from oxygen, nitrogen and sulfurincludes 5-7 membered monocyclic heteroaryl comprising 1-2 of heteroatomselected from oxygen, nitrogen and sulfur or partially or completelysaturated one thereof.

5-7 membered monocyclic heteroaryl comprising 1-2 of heteroatom selectedfrom oxygen, nitrogen and sulfur includes, for example, pyrrole,imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine,azepine, diazepine, furan, pyran, oxepin, thiophene, thiain (thiopyran),thiepin, oxazole, isoxazole, thiazole, isothiazole, oxazine, oxazepine,thiazine, thiazepine, etc.

Partially or completely saturated 5-7 membered monocyclic heteroringcomprising 1-2 of heteroatom selected from oxygen, nitrogen and sulfurincludes, for example, pyrroline, pyrrolidine, imidazoline,imidazolidine, pyrazoline, pyrazolidine, dihydropyridine,tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyrazine,piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine,dihydropyridazine, tetrahydropyridazine, perhydropyridazine,dihydroazepine, tetrahydroazepine, perhydroazepine, dihydrodiazepine,tetrahydrodiazepine, perhydrodiazepine, dihydrofuran, tetrahydrofuran,dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene,dihydrothiain (dihydrothiopyran), tetrahydrothiain(tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole,dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole,tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole,tetrahydrooxazepine, perhydrooxazepine, tetrahydrothiazepine,perhydrothiazepine, morpholine, thiomorpholine, dioxolane, dioxane,dithiolane, dithiane ring, etc.

Above 5-7 membered monocyclic heteroring includes N-oxide compound whosenitrogen is oxidized.

In the present specification, 3-10 membered monocyclic heteroringcomprising 1-2 of heteroatom selected from oxygen, nitrogen and sulfurincludes, for example, completely saturated 3-10 membered mono-cyclicheteroaryl comprising 1-2 of heteroatom selected from oxygen, nitrogenand sulfur.

Completely saturated 3-10 membered monocyclic heteroaryl comprising 1-2of heteroatom includes, for example, pyrrolidine, imidazolidine,pyrazolidine, piperidine, piperazine, perhydropyrimidine,perhydropyridazine, perhydroazepine, perhydrodiazepine, tetrahydrofuran,tetrahydropyran, tetrahydrothiophene, tetrahydrothiain(tetrahydrothiopyran), tetrahydrooxazole, tetrahydroisoxazole,tetrahydrothiazole, tetrahydroisothiazole, perhydrooxazepine,perhydrothiazepine, morpholine, thiomorpholine, dioxolane, dioxane,dithiolane, dithiane ring, etc.

Above 3-10 membered mono-cyclic heteroring includes N-oxide compoundswhose nitrogen is oxidized.

In the present specification, C3-15 mono-, bi- or tri-cyclic (fused orspiro)carboring, includes, for example, cyclopropane, cyclobutane,cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane,cyclodecane, cycloundecane, cyclododecane, cyclotridodecane,cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene,cyclohexadiene, cycloheptadiene, cyclooctadiene, benzene, indene,naphthalene, indan, tetrahydronaphthalene, bicyclo[3.3.0]octane,bicyclo[4.3.0]nonane, bicyclo[4.4.0]decane, spiro[4.4]nonane,spiro[4.5]decane, spiro[5,5]undecane, fluorene, anthracene,9,10dihydroanthracene, bicyclo[3.1.1]heptane, bicyclo[3.3.1]-2-heptene,adamantan, noradamantan, bicyclo[2.2.2]octane, etc.

In the present specification, 3-15 membered mono-, bi- or tri-cyclic(fused or spiro)heteroring including 1-4 of heteroatom selected fromoxygen, nitrogen and sulfur includes, for example, partially orcompletely saturated 3-15 membered mono-, bi- or tri-cyclic (fused orspiro)heteroaryl comprising 1-4 of heteroatom selected from oxygen,nitrogen and sulfur.

3-15 membered mono-, bi- or tri-cyclic (fused or spiro)heteroarylcomprising 1-4 of heteroatom selected from oxygen, nitrogen and sulfurincludes, for example, pyrrole, imidazole, triazole, tetrazole,pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine,diazepine, furan, pyran, oxepin, thiophene, thiain (thiopyran), thiepin,oxazole, isoxazole, thiazole, isothiazole, furazane, oxadiazole,oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine,thiadiazine, thiazepine, thiadiazepine, indole, isoindole, benzofuran,isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline,isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline,cinnoline, benzoxazole, benzothiazole, benzoimidazole,pyrazolo[5,4-b]pyridine, benzoxepin, benzooxazepine, benzooxadiazepine,benzothiepin, benzothiazepine, benzothiadiazepine, benzoazepine,benzodiazepine, benzofurazane, benzothiadiazole, benzotriazole,carbazole, acridine, dibenzofuran, dibenzothiophene, phenothiazine, etc.

Partially or completely saturated 3-15 membered mono-, bi- or tri-cyclic(fused or spiro)heteroaryl comprising 1-4 of heteroatom selected fromoxygen, nitrogen and sulfur includes, for example, pyrroline,pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine,triazoline, triazolidine, tetrazoline, tetrazolidine, dihydropyridine,tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyrazine,piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine,dihydropyridazine, tetrahydropyridazine, perhydropyridazine,dihydroazepine, tetrahydroazepine, perhydroazepine, dihydrodiazepine,tetrahydrodiazepine, perhydrodiazepine, dihydrofuran, tetrahydrofuran,dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene,dihydrothiain (dihydrothiopyran), tetrahydrothiain(tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole,dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole,tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole,dihydrooxadiazole, tetrahydrooxadiazole, dihydrothiodiazole,tetrahydrothiodiazole, tetrahydrooxadiazine, tetrahydrothiadiazine,tetrahydrooxazepine, tetrahydrooxadiazepine, perhydrooxazepine,perhydrooxadiazepine, tetrahydrothiazepine, tetrahydrothiadiazepine,perhydrothiazepine, perhydrothiadiazepine, morpholine, thiomorpholine,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzooxazole, perhydrobenzooxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzoimidazole, perhydrobenzoimidazole,dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole,dihydroacridine, tetrahydroacridine, perhydroacridine,dihydrodibenzofuran, dihydrodibenzothiophene, tetrahydrodibenzofuran,tetrahydrodibenzothiophene, perhydrodibenzofuran,perhydrodibenzothiophene, dioxolane, dioxane, dithiolane, dithian,benzodioxalane, benzodioxane, benzodithiolane, benzodithian,2,4,6-trioxaspiro[bicycle[3.3.0]octane-3,1′-cyclohexane]1,3-dioxolano[4,5-g]chromene,2-oxabicyclo[2.2.1]heptane, etc.

Above 3-15 membered mono-, bi- or tri-cyclic (fused or spiro)heteroringincludes N-oxide compounds whose nitrogen is oxidized.

In the present specification, amino acid in —CO—(NH-amino acidresidue-CO)_(n)—OH represents natural amino acid or abnormal amino acid,for example, glycine, alanine, valine, leucine, isoleucine, serine,threonine, cysteine, methionine, proline, asparagine, glutamine,phenylalanine, tyrosine, tryptophan, aspartic acid, glutamic acid,lysine, arginine, histidine, β-alanine, cystathionine, cystine,homoserine, isoleucine, lanthionine, norleucine, norvaline, ornithine,sarcosine, thyronine, etc.

Also, —CO—(NH-amino acid residue-CO)_(n)—OH includes a carboxy groupesterified by C1-8 alkyl.

Unless otherwise indicated, all isomers are included in the presentinvention. For example, the alkyl group, the alkoxy group and thealkylene group include straight-chain groups and branched-chain groups.Moreover, isomers in a double bond, a ring, a fused ring (E-, Z-, cis-,trans-isomer), isomers due to the presence of an asymmetric carbonatom(s), etc. (R-, S-isomer, α-, β-isomer, enantiomer, diastereomer),optically active isomers having optical rotation (D-, L-, d-, 1-isomer),polar compounds separated by chromatography (more polar compound, lesspolar compound), equilibrium compounds, mixtures thereof at arbitraryratios and racemic mixtures are included in the present invention.

According to the present invention, unless otherwise indicated, as isapparent for those skilled in the art, symbol

indicates that it is bound to the behind the sheet (namelyα-configuration), symbol

indicates that it is bound to the front of the sheet (namelyβ-configuration), symbol

indicates that it is α-, β- or a mixture thereof, and symbol

indicates that it is a mixture of α-configuration and β-configuration.

In the compound of formula (I), the compound wherein dashed line a is adouble bond, dashed line b is a bond, R⁹ is hydrogen, and R⁶ does notexist, i.e. the compound of formula (Ia) and the compound wherein dashedline a is a bond, dashed line b is a double bond, R⁶ is hydrogen, R⁹does not exist, i.e. the compound of formula (Ib) are tautomers.

(wherein all symbols have the same meanings as hereinbefore.)

Also, the compound of above formula (Ia) includes the following compoundof formula (Ia′), the compound of formula (Ia″) and mixture thereof

(wherein all symbols have the same meaning as hereinbefore.)

The compound of formula (I) can be converted into a pharmacologicallyacceptable salt by known methods.

Non-toxic and water-soluble salts are preferable as thepharmacologically acceptable salt.

In the present specification, the nontoxic salt includes alkaline metal(e.g. potassium, sodium, etc.) salts, alkaline earth metal (e.g.,calcium, magnesium, etc.) salts, ammonium salts (tetramethylammoniumsalt, tetrabutylammonium salt, etc.), amine (triethylamine, methylamine,dimethylamine, cyclopentylamine, benzylamine, phenethylamine,piperidine, monoethanolamine, diethanolamine,tris(hydroxymethyl)methylamine, lysine, arguinine, N-methyl-D-glucamine,etc.) salts, acid-addition salts (inorganic acid salts such ashydrochloride, hydrobromate, hydroiodate, sulfate, phosphate, andnitrate; and organic acid salts such as acetate, lactate, tartarate,benzoate, citrate, methane sulfonate, ethane sulfonate, benzenesulfonate, toluene sulfonate, isethionate, glucuronate, and gluconate),and the like.

The salt is preferably non-toxic and water-soluble. Appropriate saltsinclude salts of alkali metals (e.g., potassium, sodium, etc.), salts ofalkaline earth metals (e.g., calcium, magnesium, etc.), ammonium salts,and pharmaceutically acceptable organic amines (e.g.,tetramethylammonium, triethylamine, methylamine, dimethylamine,cyclopentylamine, benzylamine, phenethylamine, piperidine,monoethanolamine, diethanolamine, tris(hydroxymethyl)aminomethane,lysine, arginine, N-methyl-D-glucamine, etc.).

The acid-addition salt is preferably nontoxic and water-soluble.Appropriate acid-addition salts include inorganic acid salts such ashydrochloride, hydrobromate, hydroiodate, sulfate, phosphate, andnitrate; and organic acid salts such as acetate, lactate, tartarate,benzoate, citrate, methane sulfonate, ethane sulfonate, benzenesulfonate, toluene sulfonate, isethionate, glucuronate, and gluconate.

Also, the compound of the present invention represented by formula (I)or a salt thereof can be converted into a solvate by known methods.

Pharmacologically acceptable salts include solvates, or solvates ofabove alkali (alkaline-earth) metal salts, ammonium salts, organic aminesalts, acid-addition salts.

The solvates are preferably non-toxic and water-soluble. Appropriatesolvates include, for example, solvates of water, alcohols (e.g. ethanoletc.).

In the formula (I), R¹ and R² are preferably, C1-8 alkyl, morepreferably methyl.

In the formula (I), Z is preferably, —CR³R⁴—, —O— or a bond, morepreferably —CR³R⁴- or a bond.

In the formula (I), R³ and R⁴ are preferably, hydrogen or C1-8 alkyl,more preferably hydrogen or methyl.

In the formula (I), R⁵ and R⁶ are preferably, hydrogen.

In the formula (I), Cyc4 is preferably, C5-7 monocyclic carbon atom,more preferably benzene.

In the formula (I), ring is preferably C3-15 mono- or bi-cycliccarboring or 3-15 memvered mono- or bi-cyclic heteroring comprisingmono- or bi-cyclic heteroring, more preferably benzene, cyclohexane,cycloheptane, adamantan, naphthalene, quinoline, isoquinoline,piperidine or pyridine.

In the compound of formula (I), preferable compounds are the compound offormula (Ia′-1)

(wherein all symbols have the same meanings as hereinbefore.), thecompound of formula (Ia′-2)

(wherein all symbols have the same meanings as hereinbefore.), thecompound of formula (Ia′-3)

(wherein all symbols have the same meanings as hereinbefore.), thecompound of formula (Ia′-4)

(wherein all symbols have the same meanings as hereinbefore.), thecompound of formula (Ia′-5)

(wherein all symbols have the same meanings as hereinbefore.), and thecompound of formula (Ia′-6)

(wherein all symbols have the same meanings as hereinbefore.).

Concretely, the compounds shown in the following tables 1-96, examplesand pharmacologically acceptable salts thereof are included in thepresent invention.

In the following tables, Me is methyl, Et is ethyl, Boc ist-butoxycarbonyl, R¹³² is R¹⁷ or R^(17′), Ac is acetyl, i-Bu isisobutyl, c-Pr is cyclopropyl, and the other symbols have the samemeanings as above.

TABLE 1 (Ia′-1-1)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 2 (Ia′-1-2)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 3 (Ia′-1-3)

No. R¹⁷ 1 2-Me 2 3-Me 3 2-OMe 4 3-OMe 5 2-SMe 6 3-SMe 7 2-OH 8 3-OH 92-F 10 3-F 11 2-Cl 12 3-Cl 13 2-CF₃ 14 3-CF₃ 15 2-OCF₃ 16 3-OCF₃ 17 2-CN18 3-CN 19 2-COOH 20 3-COOH 21 2-acetyl 22 3-acetyl 23 2-mesyl 243-mesyl 25 2-NH₂ 26 3-NH₂ 27 2-NO₂ 28 3-NO₂ 29 2-CH₂OH 30 3-CH₂OH 312-CH₂NH₂ 32 3-CH₂NH₂ 33 2-OEt 34 3-OEt 35 2-CHO 36 3-CHO

TABLE 4 (Ia′-1-4)

No. R¹⁷ 1 Me 2 Boc 3

4 acetyl 5

6 benzoyl 7

8

9

10

11

12

13

14

15

16

17 mesyl 18

19

20

21

22

TABLE 5 (Ia′-1-5)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 6 (Ia′-1-6)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 7 (Ia′-1-7)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 8 (Ia′-1-8)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 9 (Ia′-2-1)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 10 (Ia′-2-2)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 11 (Ia′-2-3)

No. R¹⁷ 1 2-Me 2 3-Me 3 2-OMe 4 3-OMe 5 2-SMe 6 3-SMe 7 2-OH 8 3-OH 92-F 10 3-F 11 2-Cl 12 3-Cl 13 2-CF₃ 14 3-CF₃ 15 2-OCF₃ 16 3-OCF₃ 17 2-CN18 3-CN 19 2-COOH 20 3-COOH 21 2-acetyl 22 3-acetyl 23 2-mesyl 243-mesyl 25 2-NH₂ 26 3-NH₂ 27 2-NO₂ 28 3-NO₂ 29 2-CH₂OH 30 3-CH₂OH 312-CH₂NH₂ 32 3-CH₂NH₂ 33 2-OEt 34 3-OEt 35 2-CHO 36 3-CHO

TABLE 12 (Ia′-2-4)

No. R¹⁷ 1 Me 2 Boc 3

4 acetyl 5

6 benzoyl 7

8

9

10

11

12

13

14

15

16

17 mesyl 18

19

20

21

22

TABLE 13 (Ia′-2-5)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 14 (Ia′-2-6)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 15 (Ia′-2-7)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 16 (Ia′-2-8)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 17 (Ia′-3-1)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-S Me 8 3-S Me 94-S Me 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 18 (Ia′-3-2)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-S Me 8 3-S Me 94-S Me 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 19 (Ia′-3-3)

No. R¹⁷ 1 2-Me 2 3-Me 3 2-OMe 4 3-OMe 5 2-SMe 6 3-SMe 7 2-OH 8 3-OH 92-F 10 3-F 11 2-Cl 12 3-Cl 13 2-CF₃ 14 3-CF₃ 15 2-OCF₃ 16 3-OCF₃ 17 2-CN18 3-CN 19 2-COOH 20 3-COOH 21 2-acetyl 22 3-acetyl 23 2-mesyl 243-mesyl 25 2-NH₂ 26 3-NH₂ 27 2-NO₂ 28 3-NO₂ 29 2-CH₂OH 30 3-CH₂OH 312-CH₂NH₂ 32 3-CH₂NH₂ 33 2-OEt 34 3-OEt 35 2-CHO 36 3-CHO

TABLE 20 (Ia′-3-4)

No. R¹⁷ 1 Me 2 Boc 3

4 acetyl 5

6 benzoyl 7

8

9

10

11

12

13

14

15

16

17 mesyl 18

19

20

21

22

TABLE 21 (Ia′-3-5)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 22 (Ia′-3-6)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 23 (Ia′-3-7)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 24 (Ia′-3-8)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 25 (Ia′-4-1)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 26 (Ia′-4-2)

No. R¹⁷ 1 2-Me 2 3-Me 3 4-Me 4 2-OMe 5 3-OMe 6 4-OMe 7 2-SMe 8 3-SMe 94-SMe 10 2-OH 11 3-OH 12 4-OH 13 2-F 14 3-F 15 4-F 16 2-Cl 17 3-Cl 184-Cl 19 2-CF₃ 20 3-CF₃ 21 4-CF₃ 22 2-OCF₃ 23 3-OCF₃ 24 4-OCF₃ 25 2-CN 263-CN 27 4-CN 28 2-COOH 29 3-COOH 30 4-COOH 31 2-acetyl 32 3-acetyl 334-acetyl 34 2-mesyl 35 3-mesyl 36 4-mesyl 37 2-NH₂ 38 3-NH₂ 39 4-NH₂ 402-NO₂ 41 3-NO₂ 42 4-NO₂ 43 2-CH₂OH 44 3-CH₂OH 45 4-CH₂OH 46 2-CH₂NH₂ 473-CH₂NH₂ 48 4-CH₂NH₂ 49 2-OEt 50 3-OEt 51 4-OEt 52 2-CHO 53 3-CHO 544-CHO

TABLE 27 (Ia′-4-3)

No. R¹⁷ 1 2-Me 2 3-Me 3 2-OMe 4 3-OMe 5 2-SMe 6 3-SMe 7 2-OH 8 3-OH 92-F 10 3-F 11 2-Cl 12 3-Cl 13 2-CF₃ 14 3-CF₃ 15 2-OCF₃ 16 3-OCF₃ 17 2-CN18 3-CN 19 2-COOH 20 3-COOH 21 2-acetyl 22 3-acetyl 23 2-mesyl 243-mesyl 25 2-NH₂ 26 3-NH₂ 27 2-NO₂ 28 3-NO₂ 29 2-CH₂OH 30 3-CH₂OH 312-CH₂NH₂ 32 3-CH₂NH₂ 33 2-OEt 34 3-OEt 35 2-CHO 36 3-CHO

TABLE 28 (Ia′-4-4)

No. R¹⁷ 1 Me 2 Boc 3

4 acetyl 5

6 benzoyl 7

8

9

10

11

12

13

14

15

16

17 mesyl 18

19

20

21

22

TABLE 29 (Ia′-4-5)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 30 (Ia′-4-6)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 31 (Ia′-4-7)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 32 (Ia′-4-8)

No. R⁷ 1 6-Me 2 7-Me 3 6-OMe 4 7-OMe 5 6-SMe 6 7-SMe 7 6-OH 8 7-OH 9 6-F10 7-F 11 6-Cl 12 7-Cl 13 6-CF₃ 14 7-CF₃ 15 6-OCF₃ 16 7-OCF₃ 17 6-CN 188-CN 19 6-COOH 20 7-COOH 21 6-acetyl 22 7-acetyl 23 6-mesyl 24 7-mesyl25 6-NH₂ 26 7-NH₂ 27 6-NO₂ 28 7-NO₂ 29 6-CH₂OH 30 7-CH₂OH 31 6-CH₂NH₂ 327-CH₂NH₂ 33 6-OEt 34 7-OEt 35 6-CHO 36 7-CHO

TABLE 33 (Ia′-1-9)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 34 (Ia′-1-10)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 35 (Ia′-1-11)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 36 (Ia′-1-12)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 37 (Ia′-1-13)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 38 (Ia′-1-14)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 39 (Ia′-1-15)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 40 (Ia′-1-16)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 41 (Ia′-1-17)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 42 (Ia′-1-18)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 43 (Ia′-1-19)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 44 (Ia′-1-20)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 45 (Ia′-1-21)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 46 (Ia′-1-22)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 47 (Ia′-1-23)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 48 (Ia′-1-24)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 49 (Ia′-3-9)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 50 (Ia′-3-10)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 51 (Ia′-3-11)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 52 (Ia′-3-12)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 53 (Ia′-3-13)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 54 (Ia′-3-14)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 55 (Ia′-3-15)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 56 (Ia′-3-16)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 57 (Ia′-3-17)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 58 (Ia′-3-18)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 59 (Ia′-3-19)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 60 (Ia′-3-20)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 61 (Ia′-3-21)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 62 (Ia′-3-22)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 63 (Ia′-3-23)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 64 (Ia′-3-24)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 65 (Ia′-5-9)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 66 (Ia′-5-10)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 67 (Ia′-5-11)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 68 (Ia′-5-12)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 69 (Ia′-5-13)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 70 (Ia′-5-14)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 71 (Ia′-5-15)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 72 (Ia′-5-16)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 73 (Ia′-5-17)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 74 (Ia′-5-18)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 75 (Ia′-5-19)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 76 (Ia′-5-20)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 77 (Ia′-5-21)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 78 (Ia′-5-22)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 79 (Ia′-5-23)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 80 (Ia′-5-24)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 81 (Ia′-6-9)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 82 (Ia′-6-10)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 83 (Ia′-6-11)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 84 (Ia′-6-12)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 85 (Ia′-6-13)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 86 (Ia′-6-14)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 87 (Ia′-6-15)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 88 (Ia′-6-16)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 89 (Ia′-6-17)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 90 (Ia′-6-18)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 91 (Ia′-6-19)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 92 (Ia′-6-20)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 93 (Ia′-6-21)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 94 (Ia′-6-22)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 95 (Ia′-6-23)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

TABLE 96 (Ia′-6-24)

No. R¹³² 1 3-CN 2 3-NHAc 3 3-NH₂ 4 3-MeO 5 3-NHCO₂Me 6 3-NHSO₂Me 73-NHCONH₂ 8 3-NHCHO 9 3-CONHMe 10 3-NHCO-i-Bu 11 3-NHCO-c-Pr 123-NHCOCH₂OMe 13

14

15

16

17

18

19

20 4-CN 21 4-NHAc 22 4-NH₂ 23 4-MeO 24 4-NHCO₂Me 25 4-NHSO₂Me 264-NHCONH₂ 27 4-NHCHO 28 4-CONHMe 29 4-NHCO-i-Bu 30 4-NHCO-c-Pr 314-NHCOCH₂OMe 32

33

34

35

36

37

38

Methods for the Preparation of the Compound of the Present Invention:

The compound of formula (I) of the present invention may be prepared bythe following method or the methods described in the examples.

-   [1] In the compound of formula (I) of the present invention, the    compound wherein R⁶ is hydrogen, i.e. the compound of formula (IA)

(wherein all symbols have the same meaning as hereinbefore.) may beprepared by the method of the following [a], [b] or [c].

-   [a]The compound of formula (IA) may be prepared by subjecting to a    reaction the compound of formula (II)

(wherein Z¹ is —CR³⁻¹R⁴⁻¹, —O—, —S— or a bond, R¹⁻¹, R²⁻¹, R³⁻¹, R⁴⁻¹,R⁷⁻¹ and R⁸⁻¹ are each the same meaning as R¹, R², R³, R⁴, R⁷ and R⁸respectively, and hydroxy, amino or carboxy included in R¹⁻¹, R²⁻¹,R³⁻¹, R⁴⁻¹ and R⁸⁻¹ are protected if necessary.) and the compound offormula (III)

has the same meaning as ring, and hydroxy, amino or carboxy included inthe group represented by ring' are protected if necessary.) to give thecompound of formula (IA′)

(wherein all symbols have the same meaning as hereinbefore.), optionallyfollowed by subjecting it to a deprotection reaction of protectivegroups.

The reaction of the compound of formula (II) and the compound of formula(III) is known, for example, it is carried out in a concentratedsulfuric acid by subjecting to a reaction the compound of formula (II)and the compound of formula (III) at a temperature between −20 and 100°C.

Deprotection reaction may be carried out by the following methods.

Deprotection reactions of protective groups of carboxy, hydroxy or aminois known, for example,

-   (1) a deprotection reaction under alkaline conditions,-   (2) a deprotection reaction under acidic conditions,-   (3) a deprotection reaction by hydration,-   (4) a deprotection reaction of silyl group, etc are known.

To describe these methods concretely,

(1) A deprotection reaction under alkaline conditions is, for example,carried out in an organic solvent (methanol, tetrahydrofuran, dioxane ora mixture thereof, etc.) using a hydroxide of alkali metals (sodiumhydroxide, potassium hydroxide, lithium hydroxide, etc.), hydroxide ofalkaline earth metals (barium hydroxide, calcium hydroxide, etc.), orcarbonates (sodium carbonate, potassium carbonate, etc.) or a solutionthereof or a mixture thereof at a temperature between 0 and 40° C.

(2) A deprotection reaction under acidic conditions is, for example,carried out in or without an organic solvent (methylene chloride,chloroform, dioxane, ethyl acetate, anisole, etc.), using an organicacid (acetic acid, trifluoroacetic acid, methanesulfonic acid, etc.) oran inorganic acid (hydrochloric acid, sulfuric acid, etc.) or a mixturethereof (hydrobromic acid/acetic acid, etc.) at a temperature between 0and 100° C.

(3) A deprotection reaction by hydration is, for example, carried out ina solvent (ethers (tetrahydrofuran, dioxane, dimethoxyethane, diethylether, etc.), alcohols (methanol, ethanol, etc.), benzenes (benzene,toluene, etc.), ketones (acetone, methyl ethyl ketone, etc.), nitriles(acetonitrile etc.), amides (dimethylformamide etc.), water, ethylacetate, acetic acid or a mixture of more than two from above etc.) inthe presence of a catalyst (palladium-carbon, palladium black, palladiumhydroxide, platinum oxide, Raney nickel, etc.) under atmosphere ofhydrogen of normal or suppressed pressure, or in the presence ofammonium formate at a temperature between 0 and 200° C.

(4) A deprotection reaction of silyl group is, for example, carried outin a water-miscible organic solvent (tetrahydrofuran, acetonitrile,etc.) using tetrabutylammonium fluoride at a temperature between 0 and40° C.

Protective groups for carboxy include, for example, methyl, ethyl,t-butyl and benzyl.

Protective groups for hydroxy include, for example, methoxymethyl,2-tetrahydropyranyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, acetyland benzyl.

Protective groups for amino include, for example, benzyloxycarbonyl,t-butoxycarbonyl, trifluoroacetyl and 9-fluorenylmethoxycarbonyl.

Protective groups for carboxy, hydroxy or amino are not limited to abovelisted, but other groups may also be used instead, if easily andselectively eliminated. For example, the groups described in T. W.Greene, Protective Groups in Organic Synthesis 3rd edition, Wiley, NewYork, 1999 may be used.

As easily understood by those skilled in the art, the compounds of thepresent invention may be easily prepared by these reactions.

-   [b] The compound of formula (IA) may be prepared by subjecting to a    reaction the compound of formula (IV)

(wherein all symbols have the same meaning as hereinbefore.) and thecompound of formula (V)

(wherein X is halogen, and the other symbols have the same meaningshereinbefore.), optionally followed by subjecting to a deprotectionreaction of a protective group.

The reaction of the compound of formula (IV) and the compound of formula(V) is known, for example, it is carried out in an organic solvent(xylene, toluene, benzene, acetonitrile, tetrahydrofuran, methylenechloride, chloroform, etc.) in the presence of a phosphine reagent(triphenylphosphine, tributylphosphine, etc.) or phosphate reagents(trimethylphosphite, triethylphosphite, tripropylphosphite,tributylphosphite, etc.) and a base (triethylamine,diisopropylethylamine, dimethylaminopyridine, etc.) at a temperaturebetween 30° C. to refluxing temperature.

Deprotective reactions of protective groups are carried out according tothe methods described hereinbefore.

-   [c] In the compound of formula (IA), the compound wherein R⁵ is    hydrogen, i.e. the compound of formula (IA-1)

(wherein all symbols have the same meaning as hereinbefore.) may beprepared by subjecting to a reaction the compound of formula (VI)

(wherein all symbols have the same meaning as hereinbefore) and thecompound of formula (VII)

(wherein all symbols have the same meaning as hereinbefore.) to give thecompound of formula (IA′-1)

(wherein all symbols have the same meaning as hereinbefore), optionallyfollowed by subjecting to a deprotection reaction of protective group.

The reaction of the compound of formula (VI) and the compound of formula(VII) is known, for example, it is carried out in an inert organicsolvent (tetrahydrofuran (THE), diethyl ether, benzene, etc.) in thepresence of a base (lithium diisopropylamine (LDA), lithiumhexamethyldisilazide (LHMDS), n-butyl lithium, t-butyl lithium, etc.) ata temperature between −78° C. and room temperature.

The deprotection reaction of protective groups are carried out by thesame method as described hereinbefore.

-   [2] In the compound of formula (I), the compound wherein R⁵ and R⁶    are C1-8 alkyl or taken together with the carbon atom to which they    are attached to form Cyc1, i.e. the compound of formula (IB)

(wherein R⁵⁻¹ and R⁶⁻¹ are each independently, C1-8 alkyl, but R⁵⁻¹ andR⁶⁻¹ are taken together with the carbon atom to which they are attachedto form Cyc1 and the other symbols have the same meaning ashereinbefore).

The compound of formula (IB) may be prepared by subjecting to a reactionthe compound of formula (IA′-1) and the compound of formula (VIII)R¹³³-X  (VIII)(wherein R¹³³ is C1-8 alkyl and the other symbols have the same meaningas hereinbefore.) or the compound of formula (IX)X—Y—X (IX)(wherein Y is —(CH₂)_(m)— (wherein m is an integer of 2-9.) and carbonatom in —(CH₂)_(m)— may be replaced by 1-2 of heteroatom selected fromoxygen, nitrogen and sulfur and when replaced by nitrogen, the nitrogenatom is protected if necessary. and Y may be substituted with R¹⁰⁻¹(wherein R¹⁰⁻¹ has the same meaning as R¹⁰, and hydroxy in R¹⁰⁻¹ isprotected if necessary.) to give the compound of formula (IB′),optionally subjecting to deprotection reaction of the protective groups.

The reaction of the compound of formula (IA′-1) and the compound offormula (VIII) or (IX) is known, for example, it is carried out in aninert organic solvent (tetrahydrofuran, diethyl ether,dimethylformamide, benzene, dioxane, etc.) in the presence of a base(sodium hydroxide, LDA, n-butyl lithium, t-butyl lithium, etc.),optionally using potassium iodide, at a temperature between −20° C. andrefluxing temperature.

The deprotection reaction of protective groups is carried out by thesame method as described hereinbefore.

-   [3] In the compound of formula (I), the compound wherein R⁷ is Cyc2,    i.e. the compound of formula (IC)

(wherein all symbols have the same meaning as hereinbefore.) may also besubstituted with the following methods.

The compound of formula (IC) may be prepared by subjecting to a reactionthe compound of formula (X)

(wherein R⁵⁻² and R⁶⁻² have the same meanings as R⁵ and R⁶ respectively,and hydroxy or amino included in R⁵⁻² and R⁶⁻² are protected ifnecessary, and the other symbols have the same meanings ashereinbefore.) and the compound of formula (XI)Cyc2′-R¹³⁴  (XI)(wherein R¹³⁴ is —B(OH)₂ or —B(C1-8 alkyl)₂, Cyc2′ has the same meaningas Cyc2, and hydroxy, amino or carboxy included in Cyc2′ is protected ifnecessary.) to give the compound of formula (IC′)

(wherein all symbols have the same meanings as hereinbefore,),optionally followed by subjecting to a deprotection reaction of theprotective groups.

The reaction of the compound of formula (X) and the compound of formula(XI) is known, for example, it is carried out in an organic solvent(benzene, dimethylformamide, dioxane, tetrahydrofuran, methanol,acetonitrile, dimethoxyethane, acetone, etc.) in the presence of a base(sodium ethylate, sodium hydroxide, potassium hydroxide, triethylamine,sodium carbonate, sodium bicarbonate, potassium carbonate, cesiumcarbonate, thalium carbonate, tripotassium phosphate, cesium fluoride,barium hydroxide, tetrabutylammonium fluoride, etc.) and a catalyst(tetrakis(triphenylphosphine)palladium (Pd(PPh₃)₄),bis(triphenylphosphine)palladium dichloride (PdCl₂(PPh₃)₂), palladiumacetate (Pd(OAc)₂), palladium black,1,1′-bis(diphenylphosphinoferrocene)dichloropalladium (PdCl₂(dppf)₂),diallylpalladium dichloride (PdCl₂(allyl)₂),phenylbis(triphenylphosphine)palladium (PhPdI(PPh₃)₂), etc.) at atemperature of between room temperature and 120° C.

The deprotection reaction of protective groups are carried out by thesame method as described hereinbefore.

-   [4] In the compound of formula (I) of the present invention, the    compound wherein at least one group selected from ring is amide or a    group including amide, i.e. the compound of formula (ID)

(wherein ring1 has the same meaning as ring, and wherein at least onegroup of ring1 is amide or a group including amide, and the othersymbols have the same meaning as hereinbefore.) may be prepared by thefollowing method.

The compound of formula (ID) may be prepared by subjecting to amidationreaction the compound of formula (XII)

(wherein ring1 has the same meaning as ring, and wherein at least onegroup selected from ring1 is amino or a group including amino, and theother amino, hydroxy or carboxy is protected if necessary.) and acorresponding compound having carboxylic acid or acid halide, optionallyfollowed by subjecting to deprotection reaction of protective groups.

Amidation reactions are known, for example,

-   (1) a method using acid halide,-   (2) a method using mixed anhydride,-   (3) a method using a condensing agent, etc.

To explain these methods concretely,

(1) The method using acid halide is, for example, carried out bysubjecting to a reaction carboxylic acid in an organic solvent(chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.)or without a solvent, and acid-halogenating agent (oxalyl chloride,thionyl chloride, etc.) at a temperature between −20° C. and refluxingtemperature, and then subjecting to a reaction thus obtained acid halidein the presence of tertiary amine (pyridine, triethylamine,dimethylaniline, dimethylaminopyridine, etc.) at a temperature between 0and 40° C. And it is also carried out by subjecting to a reaction withan acid halide by using an alkaline aqueous solution (sodium bicarbonateor sodium hydroxide, etc.) in organic solvent (dioxane, tetrahydrofuran,etc.) at a temperature between 0 and 40° C.

-   (2) The method using mixed anhydride is, for example, carried out by    subjecting to a reaction in an organic solvent (chloroform,    methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without    a solvent, in the presence of tertiary amine (pyridine,    triethylamine, dimethylaniline, dimethylaminopyridine, etc.)    carboxylic acid with acid halide (pivaloyl chloride, tosyl chloride,    mesylchloride, etc.) or acid derivative (chloroethyl formate,    chloroisobutyl formate, etc.) at a temperature between −20 and 40°    C., and then subjecting to a reaction thus obtained mixed anhydride    with amine at a temperature between 0 and 40° C.-   (3) The method using a condensing agent is carried out, for example,    in an inert organic solvent (chloroform, methylene chloride,    dimethylformamide, diethyl ether, tetrahydrofuran, etc.) or without    a solvent, in the presence or absence of a tertiary amine (pyridine,    triethylamine, dimethylaniline, dimethylaminopyridine,    N-methylmorpholine, etc.), using a condensing reagent    (1,3-dichlorohexylcarbodiimide (DCC),    1-ethyl-3-[3-(dimethylamino)propyl]carbo diimide (EDC),    1,1′-carbonyldiimizazole (CDI), 2-chloro-1-methylpyridinium iodide,    etc.) in the presence or absence of 1-hydroxybenzotriazole, by    subjecting to a reaction carboxylic acid and amine at a temperature    between 0 and 40° C.

These reactions (1), (2) and (3) are desirably carried out underatmosphere of an inert gas (argon, nitrogen, etc.) under anhydrousconditions.

Deprotection reaction of protective groups may be carried out in thesame methods as described hereinbefore described.

-   [5] In the compound of formula (I), the compound wherein at least    one group selected from ring is sulfonamide or a group comprising    sulfonamide, i.e. the compound of formula (IE) (wherein ring2 has    the same meaning as ring, and wherein at least one group selected    from ring2 is sulfonamide or a group including sulfonamide, and the    other symbols have the same meaning as hereinbefore.) may also be    prepared by the following method.

The compound of formula (IE) may be prepared by subjecting to asulfonamidation the compound of formula (XIII)

(wherein ring2′ has the same meaning as hereinbefore, and wherein atleast one of the group represented by ring2′ is amino or a groupincluding amino, and the other amino, hydroxy or carboxy is protected ifnecessary.) and a corresponding compound having sulfonic acid orsulfonyl halide, optionally followed by subjecting to deprotectionreaction of protective groups.

Sulfonamidation reaction is known, for example, it is carried out in aninert organic solvent (chloroform, dichloromethane, dichloroethane,diethyl ether, tetrahydrofuran, etc.) or without a solvent, in thepresence of acid halide (oxalyl chloride, thionyl chloride, phosphoruspentachloride, phosphorous trichloride, etc.) at a temperature between−20° C. and refluxing temperature, and then subjecting to a reactionthus given sulfonyl halide with amine in the presence of tertiary amine(isopropylethylamine, pyridine, triethylamine, dimethylaniline,dimethylaminopyridine, etc.) in an inert organic solvent (chloroform,dichloromethane, dichloroethane, diethyl ether, tetrahydrofuran, etc.)at a temperature between 0 and 40° C.

The deprotection reaction of protective groups are carried out by thesame method as described hereinbefore.

The compounds of formula (II), (III), (IV), (V), (VI), (VII), (VIII),(IX) and (XI), used as starting materials may be prepared by knownmethods or are commercially available.

For example, the compound of formula (IV) may be prepared according tothe method described in the following reaction scheme 1 or 2.

In the reaction schemes 1 and 2, LDA is lithium diisopropylamide, DPPAis diphenylphosphorylazide, Et₃N is triethylamine, PPA ispolyphosphorous acid, DPPF is 1,1′-bis(diphenylphoshophino)ferrocene,and the other symbols have the same meaning as hereinbefore

In the reaction schemes 1 and 2, the compounds of formula (XIV), (XV),(XIX), (XX), (XXII), (XXV), (XXIX) and (XXX) are known or may beprepared by known methods easily.

In each reaction in the present invention, the reaction products may bepurified by conventional techniques, for example, distillation undernormal or reduced pressure, high performance liquid chromatography, thinlayer chromatography or column chromatography using silica gel ormagnesium silicate. Purification may be carried out after each reaction,or after a series of reactions.

Pharmacological Effect:

It was confirmed by the following experiments that the compound offormula (I) of the present invention has an inhibitory activity againstPDE7.

In Vitro Enzyme Assay

Experimental Method:

HuT78 cells (derived from human T cell lymphocyte) were cultured inPRMI1640 medium containing 10% bovine fetus serum. 2 L of cells(approximately 8×10⁸ cells) were collected, and they were homogenized ina buffer [50 mmol/l tris hydrochloric acid buffer containing 1 mmol/ldithiothreitol (DTT), 2 mmol/l ethylenediamine tetraacetate disodium(EDTA-2Na). After centrifugation (50,000 rpm, 4° C., 1 hour), thesupernatant was collected, and filtered over 0.22 μm filter and thefiltrate was fractionated by column chromatography on MonoQ (Pharmacia,hard negative ion exchange column) using the filtrate as solubleportion. The PDE activity of the fraction eluted by the concentrationgradient of NaCl of 0-0.8 mol/L was measured using 1 μmol/l of cAMP as asubstrate. Fractions where PDE activity is not inhibited by 10 μmol/l ofrolipram (PDE selective inhibitor) are collected. As to the PDE activityof these fractions, substrate-specificity against cAMP andMichaelis-Menten constant were measured and sensitivity to rolipram wasconfirmed. Then the fractions which show specificity and high affinityto cAMP which are non-sensitive fractions to rolipram were identified asPDE7. The fractions were used as an enzyme liquor for the measurement ofPDE inhibitory activity.

PDE7 inhibitory activity of the compound of the present invention of wasevaluated by the following method. 70 μl of diluted enzyme solution, 10μl of the solution of the compound of the present invention (10% inDMSO), 10 μl of reaction buffer solution [50 mmol/l MgCl₂, 1 mg/mlbovine serum albumin, 200 mmol/l tris hydrochloric acid buffer (pH 8.0)containing 40 mmol/l 2-mercaptoethanol] in 96 well plate and it wasincubated for 30 minutes at room temperature. It was microwaved for 2.5minutes to terminate the reaction. It was centrifuged (2,000 rpm for 1minute) and thereto was added 10 μl of 1 mg/ml snake venom (Sigma, cat.V7000) and it was incubated for 30 minutes at room temperature. Theserum (50 μl) was applied to alumina column (100 μl). Purified³H-adenosine was eluted with 0.005N hydrochloric acid (80 μl) and itsradioactivity of the elute was measured.

PDE7 inhibitory activity of the present invention was evaluated by theactivity inhibitory percentage calculated from the following equation.Activity inhibitory percentage (%)=(1-radioactivity in the presence ofthe compound of the present invention/radioactivity in the absence ofthe compound of the present invention)×100

IC₅₀ values were calculated as the concentration of the compound of thepresent invention when it shows 50% inhibition of activity.

The results are shown in table 97.

TABLE 97 Example No. IC₅₀ (μM) 11(35) 0.15 11(43) 0.97 11(79) 0.7611(162) 0.37 12(7) 0.27 12(15) 1.1 58 0.023 73 0.027Inhibitory Effect of IL2 Production:Experimental Method:

Jurkat cells were cultured in RPMI1640 medium containing 10% bovinefetus serum. Collected cells were prepared to give 1×10⁶ cells/ml inRPMI1640 medium containing 2% bovine fetus serum and it was added to a96-well plate 190 μl each. It was allowed to stand for 30 minutes at 37°C. in 5% CO₂ incubator and the reaction was initiated by adding 10 μl ofstimulating substance solution [0.2 μmol/lphorbol-12-myristate-13-acetate (PMA, Sigma, cat. P8139), 20 μmol/lionomycin (Sigma, cat 10634), 20 μg/ml anti-CD28 antibody (MBL, cat.IM1376) diluted by RPMI1640 medium containing 2% bovine fetus serum] andafter incubating for approximately 20 hours the plate was centrifuged by300 g for 5 minutes and the supernatant (approximately 100 μl) wascollected. The concentration of IL-2 in the supernatant was measured byusing human IL-2 ELISA system (DIACLONE, cat. 850010192), according tothe attached method of serum.

As a result, the compound of the present invention showed adose-depending inhibitory effect against IL-2 production.

Mouse Delayed Dermatitis Model

Experimental Method:

The hair of 14-week old BALB/cAnCrj male mice (Nihon Charles River) onabdomen was shaved. The next day to all over the shaved parts was added0.1 ml of picryl chloride (PC, Tokyo Chemicals industry, cat.C0307) inethanol (0.1 ml) with pipetman to sensitize. 4 days later, 2% solutionof PC in olive oil was applied to front and back of both auricles 0.02ml/ear each to induce mouse delayed dermatitis. The width of bothauricles was measured with dial sickness gauge (Ozaki Mfg. Co., Ltd.)and the auricle edema was evaluated by calculating the average. Thecompounds of the present invention were administered orally once in asuspension of 0.5% methyl cellulose solution 30 minutes beforeinduction. The compound of the present invention showed an inhibitoryactivity against auricle edema, almost equivalent effect to cyclosporineA (Wako Pure Chemical Industries, cat. 039-16301; 50 mg) ordexamethasone 21-phosphate (Sigma, cat. D-1159, 3 mg/kg), which were setup as controls.

It was confirmed by the following experiments that the compound offormula (I) has an activity as a CB2 receptor agonist.

In Vitro Signaling Assay

Experimental Method:

Human CB2 receptors expressed CHO cells were used for the assays. Cellswere dispersed seeded in 96-well plates in a density of 5×10⁴cells/well, and were subjected to experiment the next day. Afterremoving the culture media 1 mM isobutylmethylxanthine (IBMX) solutionwas added, and cells were incubated for 10 minutes at room temperature.Next, a mixture of 10 μM forskolin and the compound of the presentinvention was added. After additional incubation for 15 minutes at roomtemperature, the culture supernatant was discarded and 200 μl of lysisreagent (attached to a cAMP EIA) was added. The amounts of cAMP of thelysate were determined by a cAMP EIA kit (Amersham) under conditions ofthe forskolin-induced cAMP production. The compound of the presentinvention was dissolved in DMSO and the solution was diluted to adjustthe final concentration of DMSO to 0.1%. IC₅₀ values were calculatedfrom the inhibitory ratio of the compound of the present inventiontoward the amount of the forskolin-induced cAMP production. By the sameexperiment using CHO cells, it was confirmed that this inhibitory effecttoward cAMP production by the compound was mediated via the human CB2receptors.

The results are shown in table 97.

TABLE 97 Ex. No. IC₅₀ (nM) 46(3) 5.3 47(4) 5.2 47(6) 4.1 57(2) 3.3Toxicity:

The toxicity of the compound of the present invention of formula (I) islow enough to use as a pharmaceutical.

INDUSTRIAL APPLICABILITY

Application to Pharmaceuticals:

The compound of the present invention inhibits PDE7, and so it isthought to be useful for the prevention and/or treatment of variousdiseases, i.e. autoimmune diseases (ulcerative colitis, Crohn's disease,rheumatism, psoriasis, multiple sclerosis, collagenosis, etc.),inflammatory diseases (obstructive pulmonary disease, sepsis,pancreatitis, sarcoidosis, nephritis, hepatitis, enteritis, etc.),allergic diseases (asthma, allergic rhinitis, allergic conjunctivitis,seasonal conjunctivitis, atopic dermatitis, etc.), rejection of organtransplants, serious graft versus host disease (GVHD), diabetic disease,osteoporosis, bone fracture, restenosis, atherosclerosis, obesity,ischemic reperfusion injury, depression, Parkinson's disease, dementia,leukemia, etc.

Also, some compounds of the present invention act on CB2 specifically,and therefore, it is thought that the compound of the present inventionis useful for the prevention and/or treatment of allergic diseases(asthma, allergic rhinitis, conjunctivitis, urticaria, food allergy,etc.), atopic dermatitis, autoimmune diseases (multiple sclerosis,colitis, etc.), rheumatism, arthritis, immunodeficiency diseases(acquired immunodeficiency syndrome, etc.), pain (postoperative pain,cancer pain, etc.), etc.

The compound of formula (I) or a non-toxic salt thereof may also beadministered as a concomitant agent in combination with other agents for

-   1) supplementing and/or reinforcement of preventive and/or treating    effect(s) of the compound,-   2) improvement in kinetics and absorption of the compound and    reduction of dose and/or-   3) reduction of side effect of the compound.

A concomitant agent of the compound of formula (I) with other agents maybe administered in a mode of compounded agent in which both componentsare compounded in a single preparation or in a mode of separatepreparations. When administration is conducted using separatepreparations, a simultaneous administration and administrations withtime difference is included. In the case of administrations with timedifference, the compound of formula (I) may be firstly administered andthen other drug may be administered, or the other drug may be firstlyadministered and then the compound of formula (I) may be administered.Each of the methods for the administration may be the same or different.

There is no particular limitation for the diseases for which theabove-mentioned concomitant agent achieves the preventive and/or thetreating effect but any disease will be acceptable so far as itsupplements and/or enforces the preventive and/or treating effect of thecompound of formula (I).

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to atopic dermatitis include, for example, steroidal agents,non-steroidal anti-inflammatory drugs (NSAID), immunosuppressants,prostaglandins, antiallergic drugs, mediator liberation inhibitors,antihistamines, forskolin drugs, other phosphodiesterase inhibitors,etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to chronic obstructive pulmonary disease and/or asthmainclude, for example, steroidal agents, β2-adrenergic receptorstimulators, leukotriene receptor antagonists, thromboxane synthaseinhibitors, thromboxane A2 receptor antagonists, mediator liberationinhibitors, antihistamines, xanthine derivatives, anticholinergicagents, cytokine inhibitors, prostaglandins, forskolin drugs, otherphosphodiesterase inhibitors, elastase inhibitors, metalloproteases,etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to allergic rhinitis include, for example, steroidal drugs,antihistamines, leukotriene receptor antagonists, prostaglandins, nitricoxide synthase inhibitors, etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to arthritis and rheumatism include, for example,metalloprotease inhibitors, non-steroidal anti-inflammatory drugs(NSAID), steroid agents, prostaglandins, immunosuppressants, etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to conjunctivitis include, for example, leukotriene receptorantagonists, antihistamines, non-steroidal anti-inflammatory drugs,prostaglandins, etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to asthma include, for example, steroidal agents,leukotriene receptor antagonists, prostaglandins, expectorants, etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to colitis include, for example, steroidal agents, nitricoxide synthase inhibitors, prostaglandins, poly(ADP-ribose)polymeraseinhibitors, elastases, interleukin-8 antagonists, etc.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to multiple sclerosis include, for example,immunosuppresants.

For example, examples of the other drug for supplementing and/orreinforcing the preventive and/or treating effect of the compound offormula (I) to pain include, for example, prostaglandins, N-type calciumchannel inhibitors, nitric oxide synthase inhibitors, etc.

Steroidal agents include the followings.

For example, external medicines include, clobetasol propionate,diflorasone diacetate, fluocinonide, monometasone furoate, betamethasonedipropionate, betamethasone butyrate propionate, betamethasone valerate,difluprednate, budesonide, diflucortolone valerate, amcinonide,halcinonide, dexamethasone, dexamethasone, dexamethasone, dexamethasone,hydrocortisone acetate, hydrocortisone lactate, hydrocortisone lactatepropionate, deprodone propionate, prednisolone valerate-acetate,fluocinolone acetonide, beclometasone dipropionate,triamcinoloneacetonide, flumetasone pivalate, alclometasonedipropionate, clobetasone butyrate, prednisolone, beclometasonepropionate, fludroxycortide, etc.

For example, internal agents and/or agents for injection include,cortisone acetate, hydrocortisone, hydrocortisone sodium phosphate,hydrocortisone sodium succinate, fludrocortisone acetate, prednisolone,prednisolone acetate, prednisolone sodium succinate, butylprednisoloneacetate, prednisolone sodium phosphate, halopredone acetate,methylprednisolone, methylprednisolone acetate, prednisolone sodiumsuccinate, triamcinolone, triamcinolone acetate, triamcinoloneacetonide, dexamethasone, dexamethasone acetate, dexamethasone sodiumphosphate, dexamethasone palmitate, paramethasone acetate,betamethasone, etc.

For example, inhalant agents include, beclomethasone, fluticasonepropionate, Budesonide, flunisolide, triamcinolone, ST-126P,ciclesonide, dexamethasone palmitate, mometasone furoate, prasteronesodium sulfate, deflazacort, methyl predonisolone, methyl predonisolonesodium succinate, etc.

Non-steroidal anti-inflammatory drugs include, for example, sasapyrine(salitylosalitylic acid), sodium salicylate, aspirin, aspirindialuminate, diflunisal, indomethacin, suprofen, ufenamate,dimethylisopropylazulene, bufexamac, felbinac, dichlofenac, tolmetinsodium, clinoril, fenbufen, nabumetone, proglumetacin maleate,indometacin farnesil, acemetacin, proglumetacin maleate, amfenac sodium,mofezolac, etodolac, ibuprofen, ibuprofenpiconol, naproxen,flurbiprofen, flurbiprofen axetil, ketoprofen, phenoprofen calcium,tiaprofenic acid, oxaprozin, pranoprofen, loxoprofen sodium,alminoprofen, zaltoprofen, mefenamic acid, aluminum mefenamate,tolfenamic acid, floctafenine, ketophenylbutazon, oxyfenbutazon,piroxicam, tenoxicam, ampiroxicam, napageln ointment, epirizole,tiaramide, hydrochloride, tinoridine hydrochloride, emorfazone,sulpyrine, migrenin, saridon, cedes G, amipylo-N, sorbon, pyrine coldpreparation, acetoaminofen, fenacetin, dimetotiazine mesilate,simetride, non-pyrine cold preparation, etc.

Immunosuppresants include, for example, Protopic (FK-506), methotrexate,cyslosporin, ascomycin, leflunomide, bucillamine, salazosulfapyridine,etc.

Prostaglandins (abbreviated as PG hereafter.) include, for example, PGreceptor agonists, PG receptor antagonists, etc.

PG receptors include, PGE receptor (EP1, EP2, EP3, EP4), PGD receptor(DP), PGF receptor (FP), PGI receptor (IP), TX receptor (TP), etc.

Mediator liberation inhibitors include, for example, tranilast, sodiumchromoglicate, amlexanox, repirinast, ibudilast, dazanolast, pemirolastpotassium, etc.

Antihistamine agents include, for example, ketotifen fumarate,mequitazine, azelastine hydrochloride, oxatomide, terfenadine,emedastine difumarate, epinastine hydrochloride, astemizole, ebastine,cetirizine hydrochloride, bepotastine, fexofenadine, loratadine,desloratadine, olopatadine hydrochloride, TAK-427, ZCR-2060, NIP-530,mometasone furoate, mizolastine, BP-294, auranofin, etc.

β₂-Adrenergic receptor agonists include, for example, fenoterolhydrobromide, salbutamol sulfate, terbutaline sulfate, formoterolfumarate, salmeterol xinafoate, isoproterenol sulfate, orciprenalinesulfate, clorprenaline sulfate, epinephrine, trimetoquinolhydrochloride, hexoprenaline sulfate, procaterol hydrochloride,tulobuterol hydrochloride, tulobuterol, pirbuterol hydrochloride,clenbuterol hydrochloride, mabuterol hydrochloride, ritodrinehydrochloride, bambuterol, dopexamine hydrochloride, meluadrinetartrate, AR-C68397, levosalbutamol, R,R-Formoterol, KUR-1246, KUL-7211,AR-C89855, S-1319, etc.

Leukotriene receptor antagonists include, for example, pranlukasthydrate, montelukast, zafirlukast, seratrodast, MCC-847, KCA-757,CS-615, YM-158, L-740515, CP-195494, LM-1484, RS-635, A-93178, S-36496,BIIL-284, ONO-4057, etc.

Thromboxane synthase inhibitors include, for example, ozagrelhydrochloride, imitrodast sodium, etc.

Thromboxane A₂ receptor antagonists include, for example, seratrodast,ramatroban, domitroban calcium hydrate, KT-2-962, etc.

Xanthine derivatives include, for example, aminophylline, theophylline,doxophylline, dipamphylline, diprophylline, etc.

Anticholinergic agents include, for example, ipratropium bromide,oxitropium bromide, flutropium bromide, cimetropium bromide, temiverine,tiotropium bromide, revatropate (UK-112166), etc.

Cytokine inhibitors include, for example, suplatast tosylate (productname IPD), etc.

Other phosphodiesterase inhibitors include, for example, PDE4inhibitors, i.e. rolipram, cilomilast (Produc Name: Alifro), Bay9-8004,NIK-616, cilomilast (BY-217), cipamphiline (BRL-61063), atizolam(CP-80633), SCH-351591, YM-976, V-11294A, PD-168787, D-4396, IC-485,etc.

Non-steroidal anti-inflammatory drugs include, for example, sasapyrine(salitylosalitylic acid), sodium salicylate, aspirin, aspirindialuminate, diflunisal, indomethacin, suprofen, ufenamate,dimethylisopropylazulene, bufexamac, felbinac, dichlofenac, tolmetinsodium, clinoril, fenbufen, nabumetone, proglumetacin maleate,indometacin farnesil, acemetacin, proglumetacin maleate, amfenac sodium,mofezolac, etodolac, ibuprofen, ibuprofenpiconol, naproxen,flurbiprofen, flurbiprofen axetil, ketoprofen, phenoprofen calcium,tiaprofenic acid, oxaprozin, pranoprofen, loxoprofen sodium,alminoprofen, zaltoprofen, mefenamic acid, aluminum mefenamate,tolfenamic acid, floctafenine, ketophenylbutazon, oxyfenbutazon,piroxicam, tenoxicam, ampiroxicam, napageln ointment, epirizole,tiaramide, hydrochloride, tinoridine hydrochloride, emorfazone,sulpyrine, migrenin, saridon, cedes G, amipylo-N, sorbon, pyrine coldpreparation, acetoaminofen, fenacetin, dimetotiazine mesilate,simetride, non-pyrine cold preparation, etc.

There is no limitation for the ratio by weight of the compound offormula (I) to other agent.

With regard to other agents, two or more members of any agent may beadministered in combination.

Such other agents which supplement and/or reinforce the preventiveand/or treating effect of the compound of formula (I) include not onlythose which have been found on the basis of the above-mentionedmechanism but also those which will be found in future.

The compound of formula (I) of the present invention, a combination ofthe compound of the present invention of formula (I) and other drug isgenerally administered systemically or topically and orally orparenterally when it is used for the above objects.

The dosages are determined depending on age, body weight, symptom,therapeutic effect, administration route, duration of the treatment andthe like. Generally, 1 mg to 1000 mg per adult is orally administeredonce to several times per day, or 1 mg to 100 mg per adult isparenterally administered (preferably by intravenous administration)once to several times per day, or continuously administered from veinfor 1 to 24 hours per day.

Since the dose changes depending on various conditions as describedabove, there are cases in which doses lower than or greater than theabove ranges may be used.

The compound of the present invention of formula (I) and concomitantagent of the compound of the present invention of formula (I) and otheragent(s) may be administered in the form of solid compositions, liquidcompositions and other compositions for oral administration, andinjections, liniments, suppositories, eye lotions, inhalants and thelike for parenteral administration.

Solid compositions for oral administration include tablets, pills,capsules, dispersible powders, granules and the like.

Capsules include hard capsules and soft capsules.

In such solid compositions, one or more active compound(s) are mixedwith at least one inert diluent such as lactose, mannitol, glucose,hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone or magnesium metasilicate aluminate. The composition mayalso contain additional substances other than the inert diluent, e.g.,lubricants such as magnesium stearate, disintegrating agents such ascellulose calcium glycolate, stabilizing agents such as lactose, andassisting agents for dissolving such as glutamic acid and asparatic acidaccording to usual methods. If necessary, the tablets or pills may becoated with film of gastric- or enteric-coating agents such as sugar,gelatin, hydroxypropyl cellulose and hydroxypropyl cellulose phthalate,or be coated with two or more films. Furthermore, capsules of absorbablematerials such as gelatin are included.

Liquid compositions for oral administration include pharmaceuticallyacceptable emulsions, solutions, syrups, elixirs and the like. In suchliquid compositions, one or more active compound(s) are contained in aninert diluent commonly used (e.g., purified water, ethanol).Furthermore, such compositions may also contain auxiliary material suchas wetting agents or suspending agents, sweetening agents, flavoringagents, flavoring agents, and preserving agents.

Other compositions for oral administration include sprays containing oneor more active compound(s) which are prepared by known methods. Suchcompositions may contain stabilizing agents such as sodium hydrogensulfate, buffering agents to give isotonicity, isotonic solutions suchas sodium chloride, sodium citrate or citric acid, in addition to inertdiluents. The processes for preparing sprays are described in U.S. Pat.Nos. 2,868,691 and 3,095,355.

Injections for parenteral administration in the present inventioninclude sterile aqueous or non-aqueous solutions, suspensions andemulsions. Aqueous solutions and suspensions include distilled water forinjection and physiological saline. Non-aqueous solutions andsuspensions include propylene glycol, polyethylene glycol, plant oilsuch as olive oil, alcohols such as ethanol, POLYSORBATE80 (registeredtrade mark), and the like. Sterile aqueous and non-aqueous solutions,suspensions and emulsions may be used as a mixture. Such compositionsmay further contain preserving agents, wetting agents, emulsifyingagents, dispersing agents, stabilizing agents (e.g., lactose), auxiliaryagents such as solubilizing auxiliary agents (e.g., glutamic acid,aspartic acid). They may be sterilized by filtration through abacteria-retaining filter, incorporation of a sterilizing agent orirradiation. For example, they may also be manufactured in the form ofsterile solid compositions which can be dissolved in sterile water orother sterile diluent for injection before use of the freeze-driedproduct.

The dosage form of eye-drops for parenteral administration include eyelotions, suspending eye lotions, emulsion eye lotions, eye lotionsdissolved when used, and eye ointments.

These eye drops are manufactured according to known methods. Forexample, the eye drops can be prepared, if necessary, by appropriatelyselecting isotonizing agents (e.g., sodium chloride, concentratedglycerine, etc.), buffering agents (e.g., sodium phosphate, sodiumacetate, etc.), surfactants (e.g., POLYSORBATE80 (product name),polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil, etc.),stabilizing agents (sodium citrate, sodium edetate, etc.), preservingagents (e.g., benzalkonium chloride, paraben, etc.), and the like. Theyare sterilized in the final step or prepared by aseptic manipulation.

The inhalants for parenteral administration include aerosols, powdersfor inhalation, and liquids for inhalation, and the liquid forinhalation may be in the form which is dissolved or suspended in wateror an appropriate medium when used.

These inhalations can be produced according to known methods.

For example, the liquids for inhalation can be prepared, if necessary,by appropriately selecting preserving agents (e.g., benzalkoniumchloride, paraben, etc.), coloring agents, buffering agents (e.g.,sodium phosphate, sodium acetate, etc.), isotonizing agents (e.g.,sodium chloride, concentrated glycerine, etc.), thickeners (e.g.,carboxyvinyl polymer, etc.), absorbefacients, and the like.

The powders for inhalation can be prepared, if necessary, byappropriately selecting lubricants (e.g., stearic acid, salts thereof,etc.), binding agents (e.g., starch, dextrin, etc.), excipients (e.g.,lactose, cellulose, etc.), coloring agents, preserving agents (e.g.,benzalkonium chloride, paraben, etc.), absorbefacients, and the like.

When the liquids for inhalation are administered, a sprayer (e.g.,atomizer, nebulizer) is usually used. When the powders for inhalationare used, an inhalation administration apparatus for powder agents isusually used.

Other compositions for parenteral administration include liquids forexternal use, endemic liniments, ointments, suppositories forintrarectal administration, pessaries for intravaginal administrationand the like containing one or more active compound(s) which can beprepared by known methods.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is explained below in detail based on ReferenceExamples and Examples; but the present invention is not limited thereto.

The solvents in the parentheses show the developing or eluting solventsand the ratios of the solvents used are by volume in chromatographicseparations or TLC. The solvents in the parentheses in NMR show thesolvents for measurement.

REFERENCE EXAMPLE 1 3-cyclohexyl-3-oxo-propanenitrile

To a solution of sodium amide (1.87 g) in tetrahydrofuran (10 ml) wasadded acetonitrile (2.72 ml) dropwise at −50-−40° C. and then theretowas added cyclohexane carboxylic acid, methyl ester (2.86 ml) and themixture was stirred for 1 hour at −20° C. The reaction mixture waspoured into cold hydrochloric acid and the mixture was extracted withethyl acetate. The extract was washed with water and brine, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=4:1) to give the title compound (0.91 g) havingthe following physical data.

TLC: Rf0.33 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 3.50 (s, 2H),2.55 (m, 1H), 2.00-1.60 (m, 5H), 1.50-1.10 (m, 5H).

EXAMPLE 1(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

To a conc. sulfuric acid (2 ml) was added the compound prepared inreference example 1 (890 mg) and to the mixture was added a solution of2-methyl-1-phenylpropan-2-ol (1061 mg) in benzene (1 ml) dropwise andthe mixture was stirred for 30 minutes at 60° C. The reaction mixturewas neutralized with an aqueous solution of sodium hydroxide undercooling with ice and it was extracted with ethyl acetate. The residuewas purified by column chromatography on silica gel (hexane:ethylacetate=9:1) to give the compound of the present invention (1170 mg)having the following physical data.

TLC: Rf0.36 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.32 (br, 1H),7.71 (dd, J=8.0, 1.5 Hz, 1H), 7.39 (ddd, J=8.0, 8.0, 1.5 Hz, 1H), 7.28(ddd, J=8.0, 8.0, 1.5 Hz, 1H), 7.16 (dd, J=8.0, 1.5 Hz, 1H), 5.64 (s,1H), 2.84 (s, 2H), 2.39 (m, 1H), 2.00-1.20 (m, 10H), 1.29 (s, 6H).

EXAMPLE 1(1)-EXAMPLE 1(81)

By the same procedure as described in example 1 using the compoundprepared in reference example 1 or a corresponding nitrile derivativeand 2-methyl-1-phenylpropan-2-ol or a corresponding alcohol derivative,the following compounds of the present invention were given.

EXAMPLE 1(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxycarbonylphenyl)ethan-1-one

TLC: Rf0.18 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.95 (br, 1H),8.10 (d, J=8.0 Hz, 2H), 7.99 (d, J=8.0 Hz, 2H), 7.83 (d, J=7.5 Hz, 1H),7.45 (dd, J=7.5, 7.5 Hz, 1H), 7.35 (dd, J=7.5, 7.5 Hz, 1H), 7.22 (d,J=7.5 Hz, 1H), 6.33 (s, 1H), 3.94 (s, 3H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclopentylethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.27 (br, 1H),7.70 (m, 1H), 7.45-7.10 (m, 3H), 5.66 (s, 1H), 2.84 (s, 2H), 2.83 (m,1H), 2.00-1.50 (m, 8H), 1.29 (s, 6H).

EXAMPLE 1(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylphenyl)ethan-1-one

TLC: Rf0.33 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.58 (br, 1H),7.70 (d, J=8.0 Hz, 1H), 7.50-7.15 (m, 7H), 5.90 (s, 1H), 2.91 (s, 2H),2.51 (s, 3H), 1.37 (s, 6H).

EXAMPLE 1(4)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-methylphenyl)ethan-1-one

TLC: Rf0.33 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.84 (br, 1H),7.90-7.70 (m, 3H), 7.50-7.15 (m, 5H), 6.32 (s, 1H), 2.90 (s, 2H), 2.42(s, 3H), 1.36 (s, 6H).

EXAMPLE 1(5)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylphenyl)ethan-1-one

TLC: Rf0.33 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.80 (br, 1H),7.86 (d, J=8.0 Hz, 2H), 7.83 (m, 1H), 7.50-7.20 (m, 3H), 7.24 (d, J=8.0Hz, 2H), 6.33 (s, 1H), 2.90 (s, 2H), 2.40 (s, 3H), 1.36 (s, 6H).

EXAMPLE 1(6)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(furan-2-yl)ethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.59 (br, 1H),7.84 (m, 1H), 7.49 (dd, J=2.0, 1.0 Hz, 1H), 7.50-7.15 (m, 3H), 7.04 (dd,J=3.5, 1.0 Hz, 1H), 6.49 (dd, J=3.5, 2.0 Hz, 1H), 6.30 (s, 1H), 2.90 (s,2H), 1.34 (s, 6H).

EXAMPLE 1(7)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-chlorophenyl)ethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.55 (br, 1H),7.72 (d, J=7.5 Hz, 1H), 7.57-7.52 (m, 1H), 7.45-7.38 (m, 2H), 7.33-7.26(m, 3H), 7.21 (dd, J=7.5, 1.0 Hz, 1H), 5.97 (s, 1H), 2.92 (s, 2H), 1.38(s, 6H).

EXAMPLE 1(8)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(thiophen-2-yl)ethan-1-one

TLC: Rf0.54 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.51 (br, 1H),7.81 (d, J=7.0 Hz, 1H), 7.64 (d, J=3.0 Hz, 1H), 7.50-7.30 (m, 3H), 7.21(d, J=7.0 Hz, 1H), 7.10 (dd, J=3.0, 3.0 Hz, 1H), 6.21 (s, 1H), 2.89 (s,2H), 1.34 (s, 6H).

EXAMPLE 1(9)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-chlorophenyl)ethan-1-one

TLC: Rf0.46 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.85 (br, 1H),7.92-7.91 (m, 1H), 7.84-7.80 (m, 2H), 7.47-7.34 (m, 4H), 7.22 (d, J=7.0Hz, 1H), 6.26 (s, 1H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(10)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclobutylethan-1-one

TLC: Rf0.43 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.34 (br, 1H),7.69 (d, J=7.0 Hz, 1H), 7.45-7.20 (m, 2H), 7.16 (d, J=7.0 Hz, 1H), 5.56(s, 1H), 3.26 (m, 1H), 2.84 (s, 2H), 2.45-1.70 (m, 6H), 1.30 (s, 6H).

EXAMPLE 1(11)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.50 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.23 (br, 1H),6.70 (d, J=8.0 Hz, 1H), 7.45-7.20 (m, 2H), 7.16 (d, J=8.0 Hz, 1H), 5.60(s, 1H), 2.84 (s, 2H), 2.45 (m, 1H), 2.00-1.30 (m, 12H), 1.29 (s, 6H).

EXAMPLE 1(12)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-chlorophenyl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.82 (br, 1H),7.91-7.87 (m, 2H), 7.81 (d, J=8.0 Hz, 1H), 7.47-7.32 (m, 4H), 7.22 (dd,J=7.5, 1.0 Hz, 1H), 6.27 (s, 1H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(13)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.48 (br, 1H),7.72 (d, J=8.0 Hz, 1H), 7.45-7.25 (m, 2H), 7.16 (d, J=8.0 Hz, 1H), 5.79(s, 1H), 2.84 (s, 2H), 2.05 (m, 3H), 1.91 (m, 6H), 1.75 (m, 6H), 1.29(s, 6H).

EXAMPLE 1(14)(Z)-2-(3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.92 (br, 1H),7.95 (m, 2H), 7.71 (d, J=7.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.32 (d, J=7.5Hz, 1H), 7.23 (dd, J=7.5, 7.5 Hz, 1H), 6.32 (s, 1H), 2.83 (s, 2H), 2.32(s, 3H), 1.37 (s, 6H).

EXAMPLE 1(15)(Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.27 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.83 (br, 1H),7.95 (m, 2H), 7.71 (d, J=8.0 Hz, 1H), 7.50-7.40 (m, 3H), 7.13 (d, J=8.0Hz, 1H), 7.01 (s, 1H), 6.30 (s, 1H), 2.85 (s, 2H), 2.39 (s, 3H), 1.35(s, 6H).

EXAMPLE 1(16)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-2-yl)ethan-1-one

TLC: Rf0.26 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.95 (br, 1H),8.46 (s, 1H), 8.07 (dd, J=8.5, 1.0 Hz, 1H), 8.00-7.80 (m, 4H), 7.60-7.20(m, 5H), 6.49 (s, 1H), 2.93 (s, 2H), 1.39 (s, 6H).

EXAMPLE 1(17)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.74 (br, 1H),7.98-7.91 (m, 2H), 7.83 (d, J=7.0 Hz, 1H), 7.45-7.29 (m, 2H), 7.21 (d,J=7.5 Hz, 1H), 6.97-6.91 (m, 2H), 6.31 (s, 1H), 3.86 (s, 3H), 2.89 (s,2H), 1.35 (s, 6H).

EXAMPLE 1(18)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-methoxyphenyl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.83 (d, J=8.0 Hz, 1H), 7.55-7.29 (m, 5H), 7.22 (d, J=7.5 Hz, 1H),7.03-6.97 (m, 1H), 6.32 (s, 1H), 3.88 (s, 3H), 2.91 (s, 2H), 1.37 (s,6H).

EXAMPLE 1(19)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-fluorophenyl)ethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.78 (br, 1H),7.98-7.91 (m, 2H), 7.81 (d, J=7.5 Hz, 1H), 7.47-7.30 (m, 2H), 7.21 (d,J=7.0 Hz, 1H), 7.14-7.05 (m, 2H), 6.27 (s, 1H), 2.90 (s, 2H), 1.36 (s,6H).

EXAMPLE 1(20)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.84 (br, 1H),7.96 (m, 2H), 7.62 (s, 1H), 7.50-7.40 (m, 3H), 7.24 (d, J=7.5 Hz, 1H),7.10 (d, J=7.5 Hz, 1H), 6.32 (s, 1H), 2.85 (s, 2H), 2.42 (s, 3H), 1.35(s, 6H).

EXAMPLE 1(21)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

TLC: Rf0.27 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.78 (br, 1H),8.50 (m, 1H), 7.90-7.80 (m, 2H), 7.75-7.65 (m, 2H), 7.55-7.15 (m, 6H),6.09 (s, 1H), 2.94 (s, 2H), 1.41 (s, 6H).

EXAMPLE 1(22)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.69 (br, 1H),7.74 (d, J=8.0 Hz, 1H), 7.67 (dd, J=8.0, 2.0 Hz, 1H), 7.43-7.29 (m, 3H),7.19 (dd, J=7.0, 0.5 Hz, 1H), 7.03-6.95 (m, 2H), 6.27 (s, 1H), 3.91 (s,3H), 2.89 (s, 2H), 1.36 (s, 6H).

EXAMPLE 1(23)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-fluorophenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.79 (br, 1H),7.86 (ddd, J=8.0, 8.0, 2.0 Hz, 1H), 7.79 (d, J=7.0 Hz, 1H), 7.45-7.30(m, 3H), 7.24-7.18 (m, 2H), 7.10 (ddd, J=11.5, 8.0, 1.0 Hz, 1H), 6.30(s, 1H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(24)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-fluorophenyl)ethan-1-one

TLC: Rf0.63 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.84 (br, 1H),7.82 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.63 (d, J=10.0 Hz, 1H),7.47-7.33 (m, 3H), 7.22 (d, J=7.5 Hz, 1H), 7.17-7.10 (m, 1H), 6.27 (s,1H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(25)

A mixture of(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-2-methyl-1-phenylethan-1-one(A) and 2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylpropan-1-one (B), which was given as a mixture of A:B=5:4.

TLC: Rf0.29 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 13.05 (br, 1H ofA), 7.92 (m, 2H of A), 7.81 (m, 1H of A), 7.60-7.10 (m, 6H of A and 9Hof B), 4.80 (q, J=7.0 Hz, 1H of B), 2.84 (s, 2H of A), 2.58 (s, 2H ofB), 2.56 (d, J=7.0 Hz, 3H of B), 2.10 (s, 3H of A), 1.27 (s, 6H of A),1.08 (s, 3H of B), 0.97 (s, 3H of B).

EXAMPLE 1(26)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-cyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.21 (br, 1H),7.99-7.94 (m, 2H), 7.82 (d, J=7.0 Hz, 1H), 7.47-7.28 (m, 5H), 7.21 (d,J=7.0 Hz, 1H), 6.35 (s, 1H), 2.91 (s, 2H), 1.80-1.30 (m, 10H).

EXAMPLE 1(27)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-cyclopentan]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.54 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.03 (br, 1H),7.98-7.93 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.47-7.29 (m, 5H), 7.23 (d,J=7.5 Hz, 1H), 6.34 (s, 1H), 2.98 (s, 2H), 1.95-1.62 (m, 8H).

EXAMPLE 1(28)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-cycloheptan]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 12.16 (br, 1H),7.99-7.94 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.47-7.29 (m, 5H), 7.20 (d,J=7.0 Hz, 1H), 6.33 (s, 1H), 2.92 (s, 2H), 1.91-1.45 (m, 12H).

EXAMPLE 1(29)(Z)-2-(3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.98 (br, 1H),7.99-7.94 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.45-7.29 (m, 5H), 7.21 (d,J=7.0 Hz, 1H), 6.36 (s, 1H), 2.90 (s, 2H), 1.70-1.58 (m, 4H), 0.95 (t,J=7.5 Hz, 6H).

EXAMPLE 1(30)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-methoxycarbonylphenyl)ethan-1-one

TLC: Rf0.19 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.91 (br, 1H),8.60 (dd, J=1.5, 1.5 Hz, 1H), 8.20-8.10 (m, 2H), 7.86 (dd, J=8.5, 1.5Hz, 1H), 7.60-7.20 (m, 4H), 6.36 (s, 1H), 3.95 (s, 3H), 2.92 (s, 2H),1.38 (s, 6H).

EXAMPLE 1(31)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-cyclobutan]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.99 (br, 1H),7.97-7.94 (m, 2H), 7.80 (d, J=7.5 Hz, 1H), 7.47-7.41 (m, 4H), 7.37-7.26(m, 2H), 6.34 (s, 1H), 3.09 (s, 2H), 2.33-2.23 (m, 2H), 2.18-2.09 (m,2H), 1.96-1.79 (m, 2H).

EXAMPLE 1(32)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(quinolin-6-yl)ethan-1-one

TLC: Rf0.22 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.99 (br, 1H),8.95 (dd, J=4.0, 1.5 Hz, 1H), 8.44 (d, J=1.5 Hz, 1H), 8.30 (dd, J=9.0,1.5 Hz, 1H), 8.27 (m, 1H), 8.15 (d, J=9.0 Hz, 1H), 7.90 (m, 1H),7.50-7.20 (m, 4H), 6.47 (s, 1H), 2.94 (s, 2H), 1.40 (s, 6H).

EXAMPLE 1(33)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,4′-3,4,5,6-tetrahydropyran]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 12.41 (br, 1H),7.99-7.94 (m, 2H), 7.83 (d, J=7.0 Hz, 1H), 7.48-7.23 (m, 6H), 6.39 (s,1H), 3.90-3.84 (m, 4H), 2.96 (s, 2H), 1.80-1.73 (m, 4H).

EXAMPLE 1(34)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,4′-1′-methylpiperidin]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.27 (chloroform:methanol=10:1); NMR (CDCl₃): δ 12.22 (br, 1H),7.98-7.95 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.46-7.41 (m, 4H), 7.34 (t,J=7.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 1H), 6.36 (s, 1H), 2.92 (s, 2H),2.73-2.69 (m, 2H), 2.53-2.45 (m, 2H), 2.38 (s, 3H), 1.81-1.77 (m, 4H).

EXAMPLE 1(35)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-trifluoromethylphenyl)ethan-1-one

TLC: Rf0.19 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.42 (br, 1H),7.75-7.15 (m, 8H), 5.82 (s, 1H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 1(36)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-trifluoromethylphenyl)ethan-1-one

TLC: Rf0.47 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.92 (br, 1H),8.21 (s, 1H), 8.12 (d, J=8.0 Hz, 1H), 7.85 (d, J=7.5 Hz, 1H), 7.70 (d,J=8.0 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.55-7.20 (m, 3H), 6.31 (s, 1H),2.93 (s, 2H), 1.39 (s, 6H).

EXAMPLE 1(37)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-trifluoromethylphenyl)ethan-1-one

TLC: Rf0.27 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.93 (br, 1H),8.03 (d, J=8.0 Hz, 2H), 7.83 (m, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.50-7.20(m, 3H), 6.30 (s, 1H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 1(38)(Z)-2-(3,3,6,8-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.46 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 12.06 (br, 1H),7.88 (m, 2H), 7.50-7.35 (m, 3H), 7.03 (s, 1H), 6.86 (s, 1H), 6.11 (s,1H), 2.79 (s, 2H), 2.65 (s, 3H), 2.34 (s, 3H), 1.30 (s, 6H).

EXAMPLE 1(39)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=2:1); NMR (CDCl₃): δ 11.89 (br, 1H),9.16 (dd, J=2.0, 0.5 Hz, 1H), 8.66 (dd, J=5.0, 2.0 Hz, 1H), 8.22 (ddd,J=8.0, 2.0, 2.0 Hz, 1H), 7.83 (m, 1H), 7.50-7.20 (m, 4H), 6.29 (s, 1H),2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 1(40)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-4-yl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=2:1); NMR (CDCl₃): δ 11.98 (br, 1H),8.72 (d, J=6.0 Hz, 2H), 7.82 (m, 1H), 7.75 (d, J=6.0 Hz, 2H), 7.50-7.20(m, 3H), 6.29 (s, 1H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 1(41)(Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 12.28 (br, 1H),7.93 (m, 2H), 7.50-7.35 (m, 3H), 7.35 (dd, J=7.0, 7.0 Hz, 1H), 6.96 (s,1H), 6.92 (d, J=7.0 Hz, 1H), 6.81 (d, J=7.0 Hz, 1H), 3.97 (s, 3H), 2.85(s, 2H), 1.34 (s, 6H).

EXAMPLE 1(42)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.28 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.84 (br, 1H),7.93 (m, 2H), 7.77 (d, J=9.0 Hz, 1H), 7.50-7.35 (m, 3H), 6.85 (dd,J=9.0, 2.5 Hz, 1H), 6.72 (d, J=2.5 Hz, 1H), 6.25 (s, 1H), 3.87 (s, 3H),2.86 (s, 2H), 1.36 (s, 6H).

EXAMPLE 1(43)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,4′-piperidin]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.14 (water:methanol:chloroform=1:10:50); NMR (CDCl₃): δ 12.40(s, 1H), 7.96 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.50-7.20 (m, 6H), 6.39(s, 1H), 3.12 (m, 4H), 2.96 (s, 2H), 1.83 (m, 4H).

EXAMPLE 1(44)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,6-dimethylphenyl)ethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.52 (br, 1H),7.64 (d, J=7.5 Hz, 1H), 7.45-6.95 (m, 6H), 5.71 (s, 1H), 2.92 (s, 2H),2.33 (s, 6H), 1.38 (s, 6H).

EXAMPLE 1(45)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-ethoxycarbonylcyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.04 (br, 1H),7.98-7.93 (m, 2H), 7.82 (d, J=8.0 Hz, 1H), 7.46-7.20 (m, 6H), 6.35 (s,1H), 4.15 (q, J=7.0 Hz, 2H), 2.98 (s, 2H), 2.55-2.42 (m, 1H), 2.03-1.50(m, 8H), 1.27 (t, J=7.0 Hz, 3H).

(This compound has two stereoisomers by the existence of a carbon towhich ethoxycarbonyl is attached. This compound corresponds to a lesspolar compound on thin layer silica gel. The more polar compoundcorresponding to this compound is described in example 1(46).)

EXAMPLE 1(46)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-ethoxycarbonylcyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.26 (br, 1H),7.98-7.90 (m, 2H), 7.82 (d, J=7.0 Hz, 1H), 7.57-7.27 (m, 5H), 7.21 (d,J=6.5 Hz, 1H), 6.34 (s, 1H), 4.15 (q, J=7.0 Hz, 2H), 2.89 (s, 2H),2.34-2.25 (m, 1H), 1.98-1.40 (m, 8H), 1.27 (t, J=7.0 Hz, 3H).

(This compound has two stereoisomers by the existence of a carbon towhich ethoxycarbonyl is attached. This compound corresponds to a morepolar compound on thin layer silica gel. The less polar compoundcorresponding to this compound is described in example 1(45).)

EXAMPLE 1(47)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclododecylethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.32 (br, 1H),7.72 (m, 1H), 7.45-7.10 (m, 3H), 5.61 (s, 1H), 2.84 (m, 2H), 2.55 (m,1H), 1.70-1.20 (m, 22H), 1.29 (s, 6H).

EXAMPLE 1(48)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-t-butylphenyl)ethan-1-one

TLC: Rf0.26 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.78 (br, 1H),7.89 (d, J=8.5 Hz, 2H), 7.82 (m, 1H), 7.45 (d, J=8.5 Hz, 2H), 7.45-7.15(m, 3H), 6.33 (s, 1H), 2.90 (m, 2H), 1.36 (s, 6H), 1.35 (s, 9H).

EXAMPLE 1(49)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-oxocyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 12.63 (br, 1H),7.96 (m, 2H), 7.87 (m, 1H), 7.50-7.20 (m, 6H), 6.45 (s, 1H), 3.04 (s,2H), 2.77 (m, 2H), 2.39 (m, 2H), 2.17 (m, 2H), 1.93 (m, 2H).

EXAMPLE 1(50)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(piperidin-4-yl)ethan-1-one

TLC: Rf0.18 (water:methanol:chloroform=1:10:50); NMR (CDCl₃): δ 11.31(br, 1H), 7.70 (m, 1H), 7.45-7.15 (m, 3H), 5.64 (s, 1H), 3.17 (dt,J=12.0, 3.5 Hz, 2H), 2.85 (s, 2H), 2.67 (dt, J=3.5, 12.0 Hz, 2H), 2.42(tt, J=12.0, 4.0 Hz, 1H), 1.86 (m, 2H), 1.68 (m, 2H), 1.30 (s, 6H).

EXAMPLE 1(51)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-isopropylphenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.78 (s, 1H),7.88 (d, J=8.0 Hz, 2H), 7.86-7.80 (m, 1H), 7.44-7.18 (m, 3H), 7.28 (d,J=8.0 Hz, 2H), 6.32 (s, 1H), 3.02-2.81 (m, 1H), 2.89 (s, 2H), 1.36 (s,6H), 1.28 (d, J=8.0 Hz, 6H).

EXAMPLE 1(52)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclooctylethan-1-one

TLC: Rf0.42 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.21 (br, 1H),7.71 (d, J=7.5 Hz, 1H), 7.45-7.20 (m, 2H), 7.16 (d, J=7.5 Hz, 1H), 5.60(s, 1H), 2.84 (s, 2H), 2.51 (m, 1H), 2.00-1.40 (m, 14H), 1.29 (s, 6H).

EXAMPLE 1(53)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-methylcyclohexyl)ethan-1-one

TLC: Rf0.44 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.36 (br, 1H),7.70 (m, 1H), 7.45-7.10 (m, 3H), 5.83 (s, 1H), 2.84 (s, 2H), 2.10-1.95(m, 2H), 1.65-1.20 (m, 8H), 1.30 (s, 6H), 1.15 (s, 3H).

EXAMPLE 1(54)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-ethylphenyl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.80 (bs, 1H),7.90-7.80 (m, 3H), 7.46-7.18 (m, 5H), 6.33 (s, 1H), 2.89 (s, 2H), 2.70(q, J=7.8 Hz, 2H), 1.36 (s, 6H), 1.27 (t, J=7.8 Hz, 3H).

EXAMPLE 1(55)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-butylphenyl)ethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.79 (bs, 1H),7.89-7.81 (m, 3H), 7.46-7.19 (m, 5H), 6.33 (s, 1H), 2.90 (s, 2H), 2.66(t, J=7.4 Hz, 2H), 1.63 (m, 2H), 1.39 (m, 2H), 1.36 (s, 6H), 0.93 (t,J=7.4 Hz, 3H).

EXAMPLE 1(56)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-phenylcyclohexyl)ethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.12 (br, 1H),7.50-7.10 (m, 9H), 5.55 (s, 1H), 2.78 (s, 2H), 2.45-2.30 (m, 2H),2.15-2.00 (m, 2H), 1.80-1.30 (m, 6H), 1.26 (s, 6H).

EXAMPLE 1(57)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-propylphenyl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.79 (bs, 1H),7.87 (d, J=8.0 Hz, 2H), 7.82 (m, 1H), 7.46-7.19 (m, 3H), 7.24 (d, J=8.0Hz, 2H), 6.33 (s, 1H), 2.90 (s, 2H), 2.64 (t, J=7.4 Hz, 2H), 1.69 (m,2H), 1.36 (s, 6H), 0.95 (t, J=7.4 Hz, 3).

EXAMPLE 1(58)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylbutan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.95-7.91 (m,2H), 7.59-7.10 (m, 7H), 4.60 (m, 1H), 2.57 (s, 2H), 2.21 (m, 1H), 1.98(m, 1H), 1.09 (s, 3H), 1.02 (t, J=8.0 Hz, 3H), 1.00 (s, 3H).

EXAMPLE 1(59)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylpentan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 8.06-7.91 (m,3H), 7.59-7.24 (m, 5H), 7.11 (m, 1H), 4.69 (dd, J=7.5, 6.0 Hz, 1H), 2.61(s, 2H), 2.20 (m, 1H), 1.85 (m, 1H), 1.40 (m, 2H), 1.05 (s, 3H), 1.00(s, 3H), 0.98 (t, J=8.0 Hz, 3H).

EXAMPLE 1(60)(Z)-cis(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylcyclohexyl)ethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.25 (br, 1H),7.70 (m, 1H), 7.45-7.10 (m, 3H), 5.65 (s, 1H), 2.83 (s, 2H), 2.50 (dt,J=11.0, 4.5 Hz, 1H), 2.28 (m, 1H), 1.90-1.10 (m, 8H), 1.29 (s, 3H), 1.28(s, 3H), 0.90 (d, J=7.0 Hz, 3H).

EXAMPLE 1(61)(Z)-trans-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylcyclohexyl)ethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.38 (br, 1H),7.71 (m, 1H), 7.45-7.10 (m, 3H), 5.60 (s, 1H), 2.84 (s, 2H), 2.00-0.90(m, 10H), 1.30 (s, 6H), 0.88 (d, J=7.5 Hz, 3H).

EXAMPLE 1(62)(Z)-trans-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-methylcyclohexyl)ethan-1-one

TLC: Rf0.39 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.27 (br, 1H),7.71 (m, 1H), 7.45-7.10 (m, 3H), 5.68 (s, 1H), 2.84 (s, 2H), 2.59 (m,1H), 2.10-1.10 (m, 9H), 1.29 (s, 6H), 0.98 (d, J=7.0 Hz, 3H).

EXAMPLE 1(63)(Z)-cis(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-methylcyclohexyl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.34 (br, 1H),7.71 (m, 1H), 7.45-7.10 (m, 3H), 5.64 (s, 1H), 2.84 (s, 2H), 2.39 (m,1H), 1.95-0.80 (m, 9H), 1.29 (s, 6H), 0.92 (d, J=6.5 Hz, 3H).

EXAMPLE 1(64)(Z)-cis-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylcyclohexyl)ethan-1-one

TLC: Rf0.43 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.30 (br, 1H),7.70 (m, 1H), 7.45-7.10 (m, 3H), 5.68 (s, 1H), 2.84 (s, 2H), 2.38 (m,1H), 2.00-1.30 (m, 9H), 1.29 (s, 6H), 0.97 (d, J=7.0 Hz, 3H).

EXAMPLE 1(65)(Z)-trans-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylcyclohexyl)ethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.3.3 (br, 1H),7.70 (m, 1H), 7.45-7.10 (m, 3H), 5.64 (s, 1H), 2.84 (s, 2H), 2.24 (tt,J=12.0, 3.5 Hz, 1H), 2.00-0.90 (m, 9H), 1.29 (s, 6H), 0.90 (d, J=6.5 Hz,3H).

EXAMPLE 1(66)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3,5-dimethylisoxazol-4-yl)ethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.55 (bs, 1H),7.68 (d, J=7.8 Hz, 1H), 7.49-7.20 (m, 3H), 5.80 (s, 1H), 2.90 (s, 2H),2.66 (s, 3H), 2.50 (s, 3H), 1.36 (s, 6H).

EXAMPLE 1(67)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-trifluoromethoxyphenyl)ethan-1-one

TLC: Rf0.54 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.83 (br, 1H),8.00-7.95 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.45 (t, J=7.5 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 7.27-7.21 (m, 3H), 6.27 (s, 1H), 2.91 (s, 2H), 1.37(s, 6H).

EXAMPLE 1(68)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.82 (br, 1H),7.95-7.92 (m, 2H), 7.75 (d, J=8.0 Hz, 1H), 7.47-7.40 (m, 3H), 7.32 (dd,J=8.0, 2.0 Hz, 1H), 7.22 (d, J=2.0 Hz, 1H), 6.23 (br, 1H), 2.88 (s, 2H),1.37 (s, 6H).

EXAMPLE 1(69)(Z)-2-(5-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.96-7.92 (m, 2H), 7.77 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H),7.48-7.42 (m, 3H), 7.32-7.26 (m, 1H), 6.31 (br, 1H), 3.03 (s, 2H), 1.39(s, 6H).

EXAMPLE 1(70)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.81 (br, 1H),7.97-7.93 (m, 2H), 7.78 (d, J=2.0 Hz, 1H), 7.48-7.43 (m, 3H), 7.41 (dd,J=8.0, 2.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 6.23 (br, 1H), 2.88 (s, 2H),1.37 (s, 6H).

EXAMPLE 1(71)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(5-methyl-2-phenyloxazol-4-yl)ethan-1-one

TLC: Rf0.37 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.65 (bs, 1H),8.11-8.08 (m, 2H), 7.96 (d, J=7.6 Hz, 1H), 7.49-7.36 (m, 5H), 7.20 (d,J=7.6 Hz, 1H), 6.72 (bs, 1H), 2.91 (s, 2H), 2.79 (s, 3H), 1.38 (s, 6H).

EXAMPLE 1(72)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.80 (br, 1H),7.96-7.93 (m, 2H), 7.51 (dd, J=9.5, 2.5 Hz, 1H), 7.48-7.41 (m, 3H),7.22-7.11 (m, 2H), 6.24 (br, 1H), 2.87 (s, 2H), 1.37 (s, 6H).

EXAMPLE 1(73)(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.96-7.92 (m, 2H), 7.82 (dd, J=8.5, 5.5 Hz, 1H), 7.48-7.40 (m, 3H), 7.04(ddd, J=8.5, 8.5, 3.0 Hz, 1H), 6.94 (dd, J=8.5, 3.0 Hz, 1H), 6.23 (br,1H), 2.90 (s, 2H), 1.38 (s, 6H).

EXAMPLE 1(74)(Z)-2-(5-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.54 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.80 (br, 1H),7.96-7.93 (m, 2H), 7.65 (d, J=8.0 Hz, 1H), 7.47-7.40 (m, 3H), 7.35-7.30(m, 1H), 7.19 (dd, J=8.0, 8.0 Hz, 1H), 6.31 (br, 1H), 2.93 (s, 2H), 1.39(s, 6H).

EXAMPLE 1(75)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methyl-2-phenylthiazol-5-yl)ethan-1-one

TLC: Rf0.37 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.56 (bs, 1H),8.00-7.97 (m, 2H), 7.77 (d, J=7.8 Hz, 1H), 7.46-7.42 (m, 4H), 7.36 (m,1H), 7.22 (d, J=7.5 Hz, 1H), 6.08 (s, 1H), 2.91 (s, 2H), 2.85 (s, 3H),1.37 (s, 6H).

EXAMPLE 1(76)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-pentylbicyclo[2.2.2]octan-1-yl)ethan-1-one

TLC: Rf0.54 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.39 (bs, 1H),7.70 (d, J=7.5 Hz, 1H), 7.36 (m, 1H), 7.28 (m, 1H), 7.16 (d, J=7.5 Hz,1H), 5.73 (s, 1H), 2.83 (s, 2H), 1.81-1.76 (m, 6H), 1.56 (s, 2H),1.44-1.38 (m, 6H), 1.28 (s, 6H), 1.23-1.16 (m, 4H), 1.11-1.07 (m, 2H),0.88 (t, J=7.0 Hz, 3H).

EXAMPLE 1(77)(Z)-trans-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-t-butylcyclohexyl)ethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.32 (bs, 1H),7.71 (d, J=7.8 Hz, 1H), 7.39 (m, 1H), 7.33 (m, 1H), 7.17 (d, J=7.2 Hz,1H), 5.64 (s, 1H), 2.84 (s, 2H), 2.05 (m, 1H), 1.92 (m, 2H), 1.86 (m,2H), 1.45 (m, 2H), 1.28 (s, 6H), 1.18-1.01 (m, 3H), 0.86 (s, 9H).

EXAMPLE 1(78)(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.80 (br, 1H),7.96 (m, 2H), 7.81 (m, 1H), 7.55-7.40 (m, 5H), 7.32 (m, 1H), 6.30 (br,1H), 1.50-1.00 (m, 12H).

EXAMPLE 1(79)(Z)-2-(spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-4,1′-cyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.45 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 12.22 (br, 1H),7.99 (m, 2H), 7.81 (m, 1H), 7.50-7.40 (m, 5H), 7.32 (m, 1H), 6.32 (br,1H), 2.20-1.00 (m, 16H).

EXAMPLE 1(80)(Z)-2-(6,7-dimethoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 11.91 (br, 1H),8.00-7.97 (m, 2H), 7.48-7.41 (m, 4H), 6.91 (s, 1H), 6.36 (s, 1H), 3.88(s, 3H), 3.83 (s, 3H), 2.84 (s, 2H), 1.28 (s, 6H).

EXAMPLE 1(81)(Z)-2-(spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-4,1′-cyclopentan]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.49 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.92 (br, 1H),7.97 (m, 2H), 7.84 (d, J=8.0 Hz, 1H), 7.55-7.30 (m, 6H), 6.33 (br, 1H),2.00-1.10 (m, 14H).

EXAMPLE 22-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-cyclopentylethan-1-one,hydrochloride

To a solution of the compound prepared in example 1(2) (1132 mg) indioxane (5 ml) was added a solution of 4M hydrogen chloride in dioxane(2 ml) at room temperature. The reaction mixture was concentrated underreduced pressure. The residue was washed with hexane to give thecompound of the present invention (1212 mg) having the followingphysical data.

TLC: Rf0.38 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 14.48 (br, 1H),7.68 (dd, J=7.5, 7.5 Hz, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.46 (dd, J=7.5,7.5 Hz, 1H), 7.34 (d, J=7.5 Hz, 1H), 4.35 (br, 2H), 3.26 (m, 1H), 3.06(s, 2H), 2.20-1.55 (m, 8H), 1.59 (s, 6H).

EXAMPLE 2(1)-EXAMPLE 2(5)

By the same procedure as described in example 2 using the compoundprepared in example 1(11), example 1(25), example 1(50), example 1(58)or example 1(59) in place of the compound prepared in example 1(2), thefollowing compounds of the present invention were given.

EXAMPLE 2(1)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-cycloheptylethan-1-onehydrochloride

TLC: Rf0.40 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 7.67 (dd, J=7.5,7.5 Hz, 1H), 7.61 (d, J=7.5 Hz, 1H), 7.45 (dd, J=7.5, 7.5 Hz, 1H), 7.34(d, J=7.5 Hz, 1H), 4.75 (br, 2H), 3.05 (s, 2H), 2.93 (m, 1H), 2.06 (m,2H), 1.85-1.50 (m, 10H), 1.58 (s, 6H).

EXAMPLE 2(2)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylpropan-1-onehydrochloride

TLC: Rf0.29 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 8.13 (m, 2H),7.78 (d, J=8.0 Hz, 1H), 7.60 (ddd, J=8.0, 8.0, 1.0 Hz, 1H), 7.55-7.35(m, 4H), 7.24 (d, J=8.0 Hz, 1H), 6.31 (q, J=7.0 Hz, 1H), 3.03 (d, J=16.5Hz, 1H), 2.85 (d, J=16.5 Hz, 1H), 1.81 (d, J=7.0 Hz, 3H), 1.71 (s, 3H),1.46 (s, 3H).

EXAMPLE 2(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(piperidin-4-yl)ethan-1-onebishydrochloride

TLC: Rf0.18 (water:methanol:chloroform=1:10:50); NMR (DMSO-d₆): δ 11.19(br, 1H), 9.02 (br, 1H), 8.75 (br, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.47(dd, J=7.5, 7.5 Hz, 1H), 7.34 (dd, J=7.5, 7.5 Hz, 1H), 7.29 (d, J=7.5Hz, 1H), 5.73 (s, 1H), 3.25 (m, 2H), 2.95-2.80 (m, 4H), 2.56 (m, 1H),1.95-1.65 (m, 4H), 1.22 (s, 6H).

EXAMPLE 2(4)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylbutan-1-onehydrochloride

TLC: Rf0.77 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.21-8.16 (m,2H), 7.87 (d, J=8.0 Hz, 1H), 7.65-7.34 (m, 5H), 7.25 (d, J=8.6 Hz, 1H),6.20 (dd, J=6.2, 5.8 Hz, 1H), 3.00 (d, J=16.6 Hz, 1H), 2.86 (d, J=16.6Hz, 1H), 2.56 (m, 1H), 2.13 (m, 1H), 1.70 (s, 3H), 1.48 (s, 3H), 1.15(t, J=7.4 Hz, 3H).

EXAMPLE 2(5)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylpentan-1-onehydrochloride

TLC: Rf0.36 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 8.20 (m, 2H),7.88 (d, J=7.6 Hz, 1H), 7.64-7.35 (m, 5H), 7.24 (d, J=7.0 Hz, 1H), 6.24(dd, J=6.0, 6.2 Hz, 1H), 3.01 (d, J=16.8 Hz, 1H), 2.83 (d, J=16.8 Hz,1H), 2.48 (m, 1H), 1.99 (m, 1H), 1.80 (m, 1H), 1.71 (s, 3H), 1.45 (s,3H), 1.35 (m, 1H), 0.99 (t, J=7.4 Hz, 3H).

REFERENCE EXAMPLE 2 1,3,3-trimethyl-3,4-dihydroisoquinoline

To a concentrated sulfuric acid (10 ml) was added a solution of2-methyl-1-phenylpropan-2-ol (7.0 g) and acetonitrile (1.62 ml) inbenzene (7.0 ml) dropwise at 0° C. and the mixture was stirred for 24hours at room temperature. The reaction mixture was neutralized byadding dropwise to a mixture of ice and a saturated aqueous solution ofsodium bicarbonate and the mixture was extracted with ethyl acetatetwice. The extract was dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was dissolved in etherand thereto was added a 5N aqueous solution of sodium hydroxide and wasextracted with 1N hydrochloric acid and a 2N hydrochloric acid. Theextract was washed with ether and thereto was added a 5N aqueoussolution of sodium hydroxide and was extracted with ether twice. Theextract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated under reduced pressure togive the title compound (2.53 g) having the following physical data.

TLC: Rf0.22 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48 (dd, J=7.5,1.5 Hz, 1H), 7.35 (dt, J=1.5, 7.5 Hz, 1H), 7.30-7.25 (m, 1H), 7.14 (d,J=7.5 Hz, 1H), 2.69 (s, 2H), 2.38 (s, 3H), 1.20 (s, 6H).

EXAMPLE 3(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-cyanophenyl)ethan-1-one

To a solution of diisopropylamine (0.43 ml) in tetrahydrofuran (5 ml)was added n-butyl lithium (1.6M in hexane, 2.15 ml) and the mixture wasstirred for 30 minute at 0° C. To the reaction mixture was added asolution of the compound prepared in reference example 2 (478 mg) intetrahydrofuran (2 ml) dropwise at −78° C. and the mixture was stirredfor 90 minutes at −78° C. To the reaction mixture was added3-cyanobenzoyl chloride (571 mg) in tetrahydrofuran (2 ml) dropwise andthen it was stirred under warming to −10° C. over a period of 90minutes. To the reaction mixture was added water and was extracted withether twice. The extract was washed with 1N hydrochloric acid, water anda saturated aqueous solution of sodium chloride successively, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=30:1→10:1) to give the compound of the presentinvention (61 mg) having the following physical data.

TLC: Rf0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.89 (br, 1H),8.22 (dd, J=1.5, 1.5 Hz, 1H), 8.17 (ddd, J=7.5, 1.5, 1.5 Hz, 1H), 7.83(d, J=7.0 Hz, 1H), 7.71 (ddd, J=7.5, 1.5, 1.5 Hz, 1H), 7.55 (dd, J=7.5,7.5 Hz, 1H), 7.47 (t, J=7.0 Hz, 1H), 7.38 (t, J=7.0 Hz, 1H), 7.24 (d,J=7.0 Hz, 1H), 6.25 (s, 1H), 2.93 (s, 2H), 1.38 (s, 6H).

EXAMPLE 3(1)-EXAMPLE 3(4)

By the same procedure as described in example 3, using 4-cyanobenzoylchloride, 2-trifluoromethoxybenzoyl chloride, 2-cyanobenzoyl chloride or3-trifluoromethoxy benzoyl chloride, the following compounds of thepresent invention were given.

EXAMPLE 3(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.96 (br, 1H),8.02 (d, J=8.5 Hz, 2H), 7.81 (d, J=7.5 Hz, 1H), 7.72 (d, J=8.5 Hz, 2H),7.47 (t, J=7.5 Hz, 1H), 7.36 (t, J=7.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 1H),6.28 (s, 1H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 3(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-trifluoromethoxyphenyl)ethan-1-one

TLC: Rf0.69 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.65 (br, 1H),7.79-7.72 (m, 2H), 7.45-7.25 (m, 5H), 7.21 (d, J=7.5 Hz, 1H), 6.12 (s,1H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 3(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-cyanophenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.76 (br, 1H),7.87 (dd, J=7.5, 1.5 Hz, 1H), 7.81 (d, J=7.0 Hz, 1H), 7.76 (dd, J=7.5,1.5 Hz, 1H), 7.62 (dt, J=1.5, 7.5 Hz, 1H), 7.52-7.42 (m, 2H), 7.34 (t,J=7.0 Hz, 1H), 7.22 (d, J=7.0 Hz, 1H), 6.21 (s, 1H), 2.92 (s, 2H), 1.39(s, 6H).

EXAMPLE 3(4)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-trifluoromethoxyphenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.87 (br, 1H),7.88-7.80 (m, 3H), 7.48-7.43 (m, 2H), 7.36 (t, J=7.5 Hz, 1H), 7.31-7.27(m, 1H), 7.23 (d, J=7.5 Hz, 1H), 6.27 (s, 1H), 2.92 (s, 2H), 1.38 (s,6H).

EXAMPLE 4(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-carboxyphenyl)ethan-1-one

To a solution of the compound prepared in example 1(1) (662 mg) in amixture of methanol (5 ml) and tetrahydrofuran (5 ml) was added a 2Naqueous solution of sodium hydroxide (5 ml) at room temperature and themixture was stirred for 3 hours at room temperature. The reactionmixture was neutralized with hydrochloric acid and the mixture wasstirred overnight. The precipitate was filtered and dried and washedwith a mixture of hexane and ethyl acetate (1/1) to give the compound ofthe present invention (575 mg) having the following physical data.

TLC: Rf0.29 (methanol:chloroform=1:10); NMR (DMSO-d₆): δ 13.12 (br, 1H),11.94 (s, 1H), 8.09 (d, 7.0 Hz, 1H), 8.09 (d, J=8.5 Hz, 2H), 7.99 (d,J=8.5 Hz, 2H), 7.52 (dd, J=7.0, 7.0 Hz, 1H), 7.39 (dd, J=7.0, 7.0 Hz,1H), 7.33 (d, J=7.0 Hz, 1H), 6.50 (s, 1H), 2.94 (s, 2H), 1.29 (s, 6H).

EXAMPLE 4(1)-EXAMPLE 4(3)

By the same procedure as described in example 4 using the compoundprepared in example 1(30), example 1(45) or example 1(46) in place ofthe compound prepared in example 1(1), the following compounds of thepresent invention were given.

EXAMPLE 4(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-carboxyphenyl)ethan-1-one

TLC: Rf0.37 (methanol:chloroform=1:10); NMR (DMSO-d₆): δ 13.10 (br, 1H),11.90 (s, 1H), 8.47 (dd, J=1.5, 1.5 Hz, 1H), 8.25 (d, J=8.0 Hz, 1H),8.10-8.00 (m, 2H), 7.65-7.30 (m, 4H), 6.47 (s, 1H), 2.94 (s, 2H), 1.29(s, 6H).

EXAMPLE 4(2)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-carboxycyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (chloroform:methanol:water=10:1:0.1); NMR (CDCl₃): δ 12.08(br, 1H), 7.97-7.94 (m, 2H), 7.83 (d, J=7.5 Hz, 1H), 7.47-7.41 (m, 4H),7.35 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 6.36 (s, 1H), 2.99 (s,2H), 2.63-2.56 (m, 1H), 2.06-1.95 (m, 2H), 1.95-1.75 (m, 4H), 1.75-1.60(m, 2H).

(This compound has two stereoisomers by the existence of a carbon towhich carboxy is attached. This compound corresponds to a less polar oneon thin layer silica gel. More polar compound of this compound isdescribed in example 4(3).)

EXAMPLE 4(3)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-carboxycyclohexane]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.32 (chloroform:methanol:water=10:1:0.1); NMR (CDCl₃): δ 12.32(br, 1H), 7.95-7.92 (m, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.44-7.42 (m, 4H),7.34 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 6.33 (s, 1H), 2.90 (s,2H), 2.40-2.29 (m, 1H), 2.02-1.91 (m, 6H), 1.52-1.43 (m, 2H).

(This compound has two stereoisomers by the existence of a carbon towhich carboxy is attached. This compound corresponds to a more polar oneon thin layer silica gel. Less polar compound of this compound isdescribed in example 4(2).)

EXAMPLE 5(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-hydroxyphenyl)ethan-1-one

To the compound prepared in example 1(18) (200 mg) was added a 47%aqueous solution of hydrobromic acid (3 ml) and the mixture was stirredfor 1 hour at 115° C. The reaction mixture was allowed to cool and wasneutralized by adding a saturated aqueous solution of sodium bicarbonatedropwise, and the mixture was extracted with ethyl acetate twice. Theextract was washed with water, dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The residue was purified bycolumn chromatography on silica gel (hexane:ethyl acetate=3:1→1:1) togive the compound of the present invention (147 mg) having the followingphysical data.

TLC: Rf0.48 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (br, 1H),7.81 (d, J=8.0 Hz, 1H), 7.53-7.25 (m, 5H), 7.21 (d, J=7.5 Hz, 1H), 6.95(dd, J=8.0, 3.0 Hz, 1H), 6.30 (s, 1H), 6.13 (br, 1H), 2.90 (s, 2H), 1.36(s, 6H).

EXAMPLE 5(1)-EXAMPLE 5(3)

By the same procedure as described in example 5 using the compoundprepared in example 1(17), example 1(22) or example 1(42) in place ofthe compound prepared in example 1(18), the following compounds of thepresent invention were given.

EXAMPLE 5(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydroxyphenyl)ethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.72 (br, 1H),7.91-7.87 (m, 2H), 7.82 (d, J=7.0 Hz, 1H), 7.42 (t, J=7.0 Hz, 1H), 7.33(t, J=7.0 Hz, 1H), 7.21 (d, J=7.0 Hz, 1H), 6.90-6.85 (m, 2H), 6.29 (s,1H), 2.89 (s, 2H), 1.35 (s, 6H).

EXAMPLE 5(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-hydroxyphenyl)ethan-1-one

TLC: Rf0.70 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.83 (d, J=7.0 Hz, 1H), 7.76 (dd, J=8.0, 1.5 Hz, 1H), 7.46 (dt, J=1.5,8.0 Hz, 1H), 7.40-7.31 (m, 2H), 7.23 (d, J=7.5 Hz, 1H), 6.94 (dd, J=8.0,1.0 Hz, 1H), 6.83 (dt, J=1.0, 8.0 Hz, 1H), 6.34 (s, 1H), 2.91 (s, 2H),1.38 (s, 6H).

EXAMPLE 5(3)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.18 (ethyl acetate:hexane=1:2); NMR (DMSO-d₆): δ 11.84 (s, 1H),10.15 (s, 1H), 8.00-7.85 (m, 3H), 7.50-7.35 (m, 3H), 6.73 (dd, J=8.5,2.5 Hz, 1H), 6.67 (d, J=2.5 Hz, 1H), 6.30 (s, 1H), 2.82 (s, 2H), 1.27(s, 6H).

EXAMPLE 62-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-2-methyl-1-phenylpropan-1-one

To a solution of(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one(277 mg; see Khim. Geterotsikl. Soedin., 7, 946-949 (1994)) intetrahydrofuran (5 ml) were added at 0° C. 62.7% sodium hydride (77 mg)and methyl iodide (0.14 ml) successively and the mixture was warmed toroom temperature and the mixture was stirred for 2 hours. To thereaction mixture were added water and a saturated aqueous solution ofammonium chloride successively and the mixture was extracted with ethylacetate. The extract was dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=10:1) to give the compound of thepresent invention (110 mg) having the following physical data.

TLC: Rf0.62 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 8.03 (m, 2H),7.37 (tt, J=7.5, 2.0 Hz, 1H), 7.26 (m, 2H), 7.20-7.00 (m, 4H), 2.65 (s,2H), 1.64 (s, 6H), 1.23 (s, 6H).

EXAMPLE 6(1)-EXAMPLE 6(3)

By the same procedure as described in example 6 using 1,4-dibromobutane,1,5-dibromopentane or 2-bromo-1-(2-bromoethoxy)ethane in place of methyliodide, the following compounds of the present invention were given.

EXAMPLE 6(1)1-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)cyclopentylphenyl ketone

TLC: Rf0.66 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 7.97 (m, 2H),7.40-6.90 (m, 7H), 2.57 (s, 2H), 2.70-2.30 (m, 4H), 1.73 (m, 4H), 1.19(s, 6H).

EXAMPLE 6(2)1-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)cyclohexylphenyl ketone

TLC: Rf0.70 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 8.09 (m, 2H),7.40-7.00 (m, 7H), 2.66 (s, 2H), 2.40-2.05 (m, 4H), 1.80-1.30 (m, 6H),1.24 (s, 6H).

EXAMPLE 6(3)4-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-3,4,5,6-tetrahydropyran-4-ylphenylketone

TLC: Rf0.41 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 8.11 (m, 2H),7.45-7.00 (m, 7H), 3.80 (m, 4H), 2.68 (s, 2H), 2.40 (m, 4H), 1.26 (s,6H).

EXAMPLE 7(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,1′-4′-hydroxycyclohexane]-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 1(49) (52 mg) inmethanol (3 ml) was added sodium borohydride (6 mg) and the mixture wasstirred for 10 minutes at room temperature. The reaction mixture waspoured into water and was extracted with ethyl acetate. The extract waswashed with brine, and dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was purified by thinlayer chromatography on silica gel (hexane:ethyl acetate=5:1), to givethe compound of the present invention (less polar 11 mg, more polar 33mg) having the following physical data.

This compound has two stereoisomers by the existence of a carbon towhich hydroxy is attached. Less polar means a compound which is in lesspolar position on thin layer silica gel and more polar means a compoundwhich is in more polar position thereon.

[Less Polar]

TLC: Rf0.33 (ethyl acetate:hexane=2:1); NMR (CDCl₃): δ 12.19 (br, 1H),7.95 (m, 2H), 7.82 (m, 1H), 7.50-7.20 (m, 6H), 6.36 (s, 1H), 4.02 (m,1H), 2.97 (s, 2H), 2.10-1.55 (m, 8H).

[More Polar]

TLC: Rf0.28 (ethyl acetate:hexane=2:1); NMR (CDCl₃): δ 12.34 (br, 1H),7.96 (m, 2H), 7.83 (m, 1H), 7.50-7.20 (m, 6H), 6.37 (s, 1H), 3.66 (m,1H), 2.89 (s, 2H), 2.00-1.40 (m, 8H).

EXAMPLE 8(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-acetylpiperidin-4-yl)ethan-1-one

To a solution of the compound prepared in example 2(3) (77 mg) andtriethylamine (0.15 ml) in dichloromethane (5 ml) was added acetylchloride at room temperature (0.02 ml) and the mixture was stirred for30 minutes at room temperature. The reaction mixture was poured intowater and was extracted with ethyl acetate. The extract was washed witha saturated aqueous solution of sodium bicarbonate, water and brine,dried over anhydrous magnesium sulfate, concentrated under reducedpressure to give the compound of the present invention (65 mg) havingthe following physical data.

TLC: Rf0.72 (water:methanol:chloroform=1:10:50); NMR (CDCl₃): δ 11.33(br, 1H), 7.69 (m, 1H), 7.45-7.15 (m, 3H), 5.62 (s, 1H), 4.65 (m, 1H),3.88 (m, 1H), 3.11 (m, 1H), 2.85 (s, 2H), 2.75-2.40 (m, 2H), 2.11 (s,3H), 2.00-1.60 (m, 4H), 1.31 (s, 6H).

EXAMPLE 8(1)-EXAMPLE 8(3)

By the same procedure as described in example 8 using the compoundprepared in example 2(3) or a corresponding amine derivative and ahalide derivative corresponding to acetyl chloride, the compounds of thepresent invention having the following physical data.

EXAMPLE 8(1)(Z)-2-(spiro[3,4-dihydro-(2H)-isoquinolin-3,4′-1′-acetylpiperidin]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.53 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 12.47(s, 1H), 7.96 (m, 2H), 7.84 (d, J=7.5 Hz, 1H), 7.50-7.20 (m, 6H), 6.42(s, 1H), 4.35 (m, 1H), 3.80-3.45 (m, 2H), 3.24 (m, 1H), 2.94 (s, 2H),2.11 (s, 3H), 1.90-1.50 (m, 4H).

EXAMPLE 8(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-t-butoxycarbonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.32 (br, 1H),7.69 (m, 1H), 7.45-7.15 (m, 3H), 5.62 (s, 1H), 4.17 (m, 2H), 2.85 (s,2H), 2.77 (m, 2H), 2.42 (tt, J=11.5, 3.5 Hz, 1H), 1.84 (m, 2H), 1.66 (m,2H), 1.47 (s, 9H), 1.30 (s, 6H).

EXAMPLE 8(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-mesylpiperidin-4-yl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=2:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.68 (m, 1H), 7.45-7.15 (m, 3H), 5.61 (s, 1H), 3.85 (m, 2H), 2.90-2.70(m, 2H), 2.86 (s, 2H), 2.81 (s, 3H), 2.42 (m, 1H), 2.05-1.80 (m, 4H),1.32 (s, 6H).

EXAMPLE 9(Z)-2-(6-phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

Under atmosphere of argon, a solution of the compound prepared inexample 1(68) (312 mg) in dimethoxyethane (120 ml) was degassed andthereto were added tetrakis(triphenylphosphine)palladium (58 mg), asaturated aqueous solution of sodium bicarbonate (2.5 ml) and benzeneboronic acid (183 mg) and the mixture was refluxed for 3 days. Thereaction mixture was allowed to cool and thereto was added water and themixture was extracted with ethyl acetate twice. The extract was washedwith water and brine, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=5:1) to give thecompound of the present invention (121 mg) having the following physicaldata.

TLC: Rf0.39 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.82 (br, 1H),7.99-7.96 (m, 2H), 7.89 (d, J=8.0 Hz, 1H), 7.66-7.63 (m, 2H), 7.58 (dd,J=8.0, 2.0 Hz, 1H), 7.51-7.38 (m, 7H), 6.36 (br, 1H), 2.98 (s, 2H), 1.41(s, 6H).

EXAMPLE 9(1)(Z)-2-(6-(pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

By the same procedure as described in example 9 using diethyl(3-pyridyl)borane in place of benzene boronic acid, the compound of thepresent invention having the following physical data was given.

TLC: Rf0.31 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (br, 1H),8.91 (d, J=1.5 Hz, 1H), 8.65 (dd, J=5.0, 1.5 Hz, 1H), 7.98-7.93 (m, 4H),7.57 (dd, J=8.0, 2.0 Hz, 1H), 7.48-7.41 (m, 5H), 6.38 (s, 1H), 2.99 (s,2H), 1.41 (s, 6H).

EXAMPLE 10(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydroxymethylphenyl)ethan-1-one

To a suspension of lithium aluminum hydride (95 mg) in anhydroustetrahydrofuran (9 ml) was added a solution of the compound prepared inexample 1(1) (317 mg) in anhydrous tetrahydrofuran (6 ml) and themixture was stirred for 1 hour at room temperature. To the reactionmixture was added a saturated aqueous solution of sodium sulfate (1.0ml) and the mixture was stirred. The reaction mixture was diluted withether, and the mixture was dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=3:1→1:1) to give thecompound of the present invention (251 mg) having the following physicaldata.

TLC: Rf0.33 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.84 (br, 1H),7.95 (d, J=8.0 Hz, 2H), 7.83 (d, J=7.0 Hz, 1H), 7.46-7.41 (m, 3H), 7.35(t, J=7.0 Hz, 1H), 7.22 (d, J=7.0 Hz, 1H), 6.33 (s, 1H), 4.76 (s, 2H),2.91 (s, 2H), 1.75 (br, 1H), 1.37 (s, 6H).

EXAMPLE 10(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-hydroxymethylphenyl)ethan-1-one

By the same procedure as described in example 10 using the compoundprepared in example 1(30) in place of the compound prepared in example1(1), the compound of the present invention having the followingphysical data.

TLC: Rf0.33 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.86 (br, 1H),7.94 (s, 1H), 7.90-7.83 (m, 2H), 7.49-7.41 (m, 3H), 7.35 (t, J=7.0 Hz,1H), 7.22 (d, J=7.0 Hz, 1H), 6.34 (s, 1H), 4.77 (s, 2H), 2.91 (s, 2H),1.77 (br, 1H), 1.37 (s, 6H).

REFERENCE EXAMPLE 3 3-(4-isopropylphenyl)-2,2-dimethylpropanoic acid

Diisopropylamine (3.08 ml) was dissolved in tetrahydrofuran (40 ml) andto the mixture was added n-butyl lithium (13.8 ml; 1.6M in hexane) at−78° C. and then was added isobutylacetate (0.93 ml) and the mixture wasstirred for 1 hour at 30° C. To the reaction mixture was added asolution of 4-isopropylbenzyl chloride (2.19 g) in tetrahydrofuran (10ml) at −78° C. and the mixture was stirred for 2 hours at roomtemperature. The reaction mixture was poured into cool hydrochloric acidand the mixture was extracted with ethyl acetate. The extract wasconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=5:1) to give the title compound (1.73g) having the following physical data.

TLC: Rf0.32 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 7.15-7.05 (m,4H), 2.88 (m, 1H), 2.86 (s, 2H), 1.23 (d, J=7.0 Hz, 6H), 1.20 (s, 6H).

REFERENCE EXAMPLE 4 2-methyl-1-(4-isopropylphenyl)propan-2-isocyanate

To dioxane (20 ml) were added the compound prepared in reference example3 (1.71 g), diphenylphosphoryl azide (2.15 g) and triethylamine (1.2 ml)and the mixture was refluxed for 1 hour. The reaction mixture wasallowed to cool and was poured into ice-water and was extracted withether. The extract was washed with brine, dried over anhydrous magnesiumsulfate and concentrated to give the title compound (1.70 g, crude). Itwas used in the next reaction without subjecting to purification.

REFERENCE EXAMPLE 53,3-dimethyl-7-isopropyl-3,4-dihydro-(2H)-isoquinolin-1-one

To the compound prepared in reference example 4(1.70 g) was addedpolyphosphoric acid (100 g) and the mixture was stirred for 2 hours atroom temperature. To the reaction mixture was added ice-water and themixture was extracted with ethyl acetate. The extract was washed withwater, a saturated aqueous solution of sodium bicarbonate and brinesuccessively, dried over anhydrous magnesium sulfate and concentrated.The residue was purified by column chromatography on silica gel to givethe title compound (60 mg) having the following physical data.

TLC: Rf0.36 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 7.94 (d, J=2.0Hz, 1H), 7.31 (dd, J=8.0, 2.0 Hz, 1H), 7.10 (d, J=8.0 Hz, 1H), 5.73 (br,1H), 2.95 (m, 1H), 2.89 (s, 2H), 1.31 (s, 6H), 1.27 (d, J=7.0 Hz, 6H).

REFERENCE EXAMPLE 63,3-dimethyl-7-isopropyl-3,4-dihydro-(2H)-isoquinolin-1-thione

To toluene (5 ml) were added the compound prepared in reference example5 (52 mg) and Lawesson reagent (48 mg) and the mixture was refluxed for1 hour. The reaction mixture was allowed to cool and was purified bycolumn chromatography on silica gel (hexane:ethyl acetate=9:1) to givethe title compound (48 mg) having the following physical data.

TLC: Rf0.35 (chloroform:hexane=1:4); NMR (CDCl₃): δ 8.39 (d, J=2.0 Hz,1H), 7.97 (br, 1H), 7.33 (dd, J=7.5, 2.0 Hz, 1H), 7.05 (d, J=7.5 Hz,1H), 2.98 (m, 1H), 2.90 (s, 2H), 1.34 (s, 6H), 1.28 (d, J=7.0 Hz, 6H).

REFERENCE EXAMPLE 73,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-one

To chloroform (30 ml) were added 2-hydroxybenzamide (2.74 g) and acetonedimethyl acetal (2.6 ml) and thereto was added conc. sulfuric acid (0.6ml) at room temperature and the mixture was refluxed for 8 hours. Thereaction mixture was allowed to cool, and the precipitate was removed.The filtrate was concentrated. To the residue was added ether, and waswashed with a 2N aqueous solution of sodium hydroxide, water and brinesuccessively, dried over anhydrous magnesium sulfate and concentrated togive the title compound having the following physical data.

TLC: Rf0.45 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 7.92 (dd, J=7.5,1.5 Hz, 1H), 7.45 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.15 (br, 1H), 7.07(ddd, J=7.5, 7.5, 1.0 Hz, 1H), 6.92 (dd, J=8.0, 1.0 Hz, 1H), 1.66 (s,6H).

REFERENCE EXAMPLE 83,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-thione

To toluene (70 ml) were added the compound prepared in reference example7 (1.20 g) and Lawesson reagent (1.37 g) and the mixture was refluxedfor 2 hours. The reaction mixture was purified by column chromatographyon silica gel (hexane:ethyl acetate=5:1) to give the title compound(1.34 g) having the following physical data.

TLC: Rf0.45 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 8.45 (br, 1H),8.31 (dd, J=8.0, 1.5 Hz, 1H), 7.46 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.07(ddd, J=8.0, 7.5, 1.0 Hz, 1H), 6.89 (dd, J=8.0, 1.0 Hz, 1H), 1.66 (s,6H).

EXAMPLE 11(Z)-2-(7-isopropyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in reference example 6 (45 mg) inxylene (5 ml) was added benzoylmethyl bromide (46 mg) and the mixturewas stirred for 1.5 hours. To the reaction mixture was addedtriethylamine (0.04 ml) and the mixture was stirred for 15 minutes. Tothe reaction mixture was added triphenylphosphine (61 mg) and themixture was stirred for 15 minutes, and then thereto was addedtriethylamine (0.04 ml) and the mixture was refluxed for 1 hour. Thereaction mixture was allowed to cool and was purified by columnchromatography on silica gel (hexane:ethyl acetate=20:1) to give thecompound of the present invention (58 mg) having the following physicaldata.

TLC: Rf0.19 (ethyl acetate:hexane=1:10); NMR (CDCl₃): δ 11.88 (br, 1H),7.96 (m, 2H), 7.64 (d, J=1.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.30 (dd,J=8.0, 1.5 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 6.32 (s, 1H), 2.98 (m, 1H),2.86 (s, 2H), 1.36 (s, 6H), 1.30 (d, J=7.0 Hz, 6H).

EXAMPLE 11(1)-EXAMPLE 11(203)

By the same procedure as described in example 11 using the compoundprepared in reference example 6 or a corresponding derivative, andbenzoylmethyl bromide or a corresponding derivative, the followingcompounds were given.

EXAMPLE 11(1)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.22 (chloroform:hexane=1:1); NMR (CDCl₃): δ 11.65 (br, 1H), 7.94(m, 2H), 7.74 (d, J=7.5, 1.5 Hz, 1H), 7.50-7.40 (m, 4H), 7.07 (ddd,J=7.5, 7.5, 1.0 Hz, 1H), 6.96 (dd, J=7.5, 1.0 Hz, 1H), 6.34 (s, 1H),1.67 (s, 6H).

EXAMPLE 11(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.20 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.82 (br, 1H),7.94 (m, 2H), 7.50-7.40 (m, 3H), 7.34 (d, J=2.5 Hz, 1H), 7.13 (d, J=8.0Hz, 1H), 6.98 (dd, J=8.0, 2.5 Hz, 1H), 6.28 (s, 1H), 3.87 (s, 3H), 2.83(s, 2H), 1.35 (s, 6H).

EXAMPLE 11(3)(Z)-2-(7-ethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.86 (br, 1H),7.96 (m, 2H), 7.63 (s, 1H), 7.50-7.40 (m, 3H), 7.27 (m, 1H), 7.12 (d,J=8.0 Hz, 1H), 6.32 (s, 1H), 2.86 (s, 2H), 2.71 (q, J=7.5 Hz, 2H), 1.36(s, 6H), 1.29 (t, J=7.5 Hz, 3H).

EXAMPLE 11(4)(Z)-2-(7-t-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.90 (br, 1H),7.95 (m, 2H), 7.81 (d, J=2.0 Hz, 1H), 7.50-7.40 (m, 4H), 7.14 (d, J=8.0Hz, 1H), 6.32 (s, 1H), 2.86 (s, 2H), 1.38 (s, 9H), 1.36 (s, 6H).

EXAMPLE 11(5)(Z)-2-(7-propyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.86 (br, 1H),7.96 (m, 2H), 7.61 (d, J=1.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.24 (dd,J=8.0, 1.5 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 6.32 (s, 1H), 2.86 (s, 2H),2.65 (t, J=7.5 Hz, 2H), 1.69 (m, 2H), 1.36 (s, 6H), 0.98 (t, J=7.5 Hz,3H).

EXAMPLE 11(6)(Z)-2-(7-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.27 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.86 (br, 1H),7.96 (m, 2H), 7.61 (d, J=2.0 Hz, 1H), 7.50-7.40 (m, 3H), 7.25 (dd,J=8.0, 2.0 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 6.31 (s, 1H), 2.86 (s, 2H),2.67 (t, J=7.5 Hz, 2H), 1.65 (m, 2H), 1.39 (m, 2H), 1.36 (s, 6H), 0.96(t, J=7.5 Hz, 3H).

EXAMPLE 11(7)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.27 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.75 (br, 1H),8.00-7.90 (m, 3H), 7.54 (dd, J=8.0, 2.0 Hz, 1H), 7.50-7.40 (m, 3H), 7.10(d, J=8.0 Hz, 1H), 6.26 (s, 1H), 2.85 (s, 2H), 1.36 (s, 6H).

EXAMPLE 11(8)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.46 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 10.98 (br, 1H),7.56 (d, J=2.5 Hz, 1H), 7.31 (dd, J=8.5, 2.5 Hz, 1H), 6.86 (d, J=2.5 Hz,1H), 5.55 (s, 1H), 2.49 (m, 1H), 1.95-1.40 (m, 12H), 1.58 (s, 6H).

EXAMPLE 11(9)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.42 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.07 (br, 1H),7.57 (d, J=2.5 Hz, 1H), 7.32 (dd, J=8.5, 2.5 Hz, 1H), 6.86 (d, J=8.5 Hz,1H), 5.59 (s, 1H), 2.32 (m, 1H), 1.95-1.15 (m, 10H), 1.59 (s, 6H).

EXAMPLE 11(10)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.20 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.40 (br, 1H),7.65 (dd, J=7.5, 2.0 Hz, 1H), 7.60 (d, J=2.5 Hz, 1H), 7.39 (m, 1H), 7.33(dd, J=8.5, 2.5 Hz, 1H), 7.05-6.95 (m, 2H), 6.89 (d, J=8.5 Hz, 1H), 6.25(s, 1H), 3.93 (s, 3H), 1.65 (s, 6H).

EXAMPLE 11(11)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.19 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.67 (br, 1H),8.01 (d, J=9.0 Hz, 2H), 7.75 (d, J=9.0 Hz, 2H), 7.67 (d, J=2.5 Hz, 1H),7.40 (dd, J=8.5, 2.5 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 6.21 (s, 1H), 1.68(s, 6H).

EXAMPLE 11(12)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.39 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.15 (br, 1H),7.40 (d, J=1.5 Hz, 1H), 7.18 (dd, J=8.5, 1.5 Hz, 1H), 6.81 (d, J=8.5 Hz,1H), 5.62 (s, 1H), 2.33 (s, 3H), 2.31 (m, 1H), 1.95-1.15 (m, 10H), 1.58(s, 6H).

EXAMPLE 11(13)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.14 (br, 1H),7.08 (d, J=3.0 Hz, 1H), 6.96 (dd, J=9.0, 3.0 Hz, 1H), 6.85 (d, J=9.0 Hz,1H), 5.57 (s, 1H), 3.83 (s, 3H), 2.32 (m, 1H), 1.95-1.15 (m, 10H), 1.58(s, 6H).

EXAMPLE 11(14)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.41 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.07 (br, 1H),7.29 (dd, J=9.0, 3.0 Hz, 1H), 7.08 (ddd, J=9.0, 8.0, 3.0 Hz, 1H), 6.88(dd, J=9.0, 5.0 Hz, 1H), 5.56 (s, 1H), 2.32 (m, 1H), 1.95-1.15 (m, 10H),1.59 (s, 6H).

EXAMPLE 11(15)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.48 (br, 1H),7.64 (dd, J=7.5, 1.5 Hz, 1H), 7.42 (d, J=2.0 Hz, 1H), 7.37 (ddd, J=8.0,7.5, 1.5 Hz, 1H), 7.19 (dd, J=8.0, 2.0 Hz, 1H), 7.01 (ddd, J=7.5, 7.5,1.0 Hz, 1H), 6.97 (dd, J=8.0, 1.0 Hz, 1H), 6.83 (d, J=8.0 Hz, 1H), 6.23(s, 1H), 3.92 (s, 3H), 2.32 (s, 3H), 1.65 (s, 6H).

EXAMPLE 11(16)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.46 (br, 1H),7.66 (dd, J=7.5, 2.0 Hz, 1H), 7.38 (ddd, J=8.0, 7.5, 2.0 Hz, 1H), 7.12(d, J=3.0 Hz, 1H), 7.05-6.95 (m, 3H), 6.87 (d, J=8.0 Hz, 1H), 6.23 (s,1H), 3.91 (s, 3H), 3.81 (s, 3H), 1.64 (s, 6H).

EXAMPLE 11(17)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.40 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.40 (br, 1H),7.67 (dd, J=7.5, 2.0 Hz, 1H), 7.39 (ddd, J=8.0, 7.5, 2.0 Hz, 1H), 7.32(dd, J=9.0, 3.0 Hz, 1H), 7.10 (ddd, J=9.0, 8.0, 3.0 Hz, 1H), 7.02 (ddd,J=7.5, 7.5, 1.5 Hz, 1H), 6.98 (dd, J=8.0, 1.5 Hz, 1H), 6.90 (dd, J=9.0,4.5 Hz, 1H), 6.25 (s, 1H), 3.93 (s, 3H), 1.65 (s, 6H).

EXAMPLE 11(18)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.49 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.07 (br, 1H),7.39 (d, J=1.5 Hz, 1H), 7.17 (dd, J=8.0, 1.5 Hz, 1H), 6.81 (d, J=8.0 Hz,1H), 5.58 (s, 1H), 2.48 (m, 1H), 2.33 (s, 3H), 2.00-1.40 (m, 12H), 1.59(s, 6H).

EXAMPLE 11(19)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.43 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.06 (br, 1H),7.07 (d, J=3.0 Hz, 1H), 6.96 (dd, J=9.0, 3.0 Hz, 1H), 6.85 (d, J=9.0 Hz,1H), 5.54 (s, 1H), 3.83 (s, 3H), 2.49 (m, 1H), 2.00-1.40 (m, 12H), 1.58(s, 6H).

EXAMPLE 11(20)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.53 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 10.98 (br, 1H),7.29 (dd, J=9.0, 3.0 Hz, 1H), 7.08 (ddd, J=9.0, 8.0, 3.0 Hz, 1H), 6.87(dd, J=9.0, 5.0 Hz, 1H), 5.53 (s, 1H), 2.48 (m, 1H), 2.00-1.40 (m, 12H),1.59 (s, 6H).

EXAMPLE 11(21)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.26 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.74 (br, 1H),8.02 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.0 Hz, 2H), 7.49 (d, J=1.5 Hz, 1H),7.26 (dd, J=8.0, 1.5 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 6.24 (s, 1H), 2.38(s, 3H), 1.67 (s, 6H).

EXAMPLE 11(22)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.16 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.72 (br, 1H),8.00 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.0 Hz, 2H), 7.17 (d, J=3.0 Hz, 1H),7.04 (dd, J=9.0, 3.0 Hz, 1H), 6.92 (d, J=9.0 Hz, 1H), 6.19 (s, 1H), 3.86(s, 3H), 1.67 (s, 6H).

EXAMPLE 11(23)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.66 (br, 1H),8.01 (d, J=8.5 Hz, 2H), 7.75 (d, J=8.5 Hz, 2H), 7.40 (dd, J=9.0, 3.0 Hz,1H), 7.17 (ddd, J=9.0, 8.0, 3.0 Hz, 1H), 6.95 (dd, J=9.0, 4.5 Hz, 1H),6.18 (s, 1H), 1.68 (s, 6H).

EXAMPLE 11(24)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.49 (br, 1H),7.68-7.63 (m, 2H), 7.42-7.35 (m, 2H), 7.05-6.93 (m, 4H), 6.30 (s, 1H),3.92 (s, 3H), 1.66 (s, 6H).

EXAMPLE 11(25)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.75 (br, 1H),8.03-7.99 (m, 2H), 7.75-7.71 (m, 3H), 7.46 (dt, J=1.5, 8.0 Hz, 1H), 7.09(t, J=8.0 Hz, 1H), 6.98 (d, J=8.0 Hz, 1H), 6.27 (s, 1H), 1.69 (s, 6H).

EXAMPLE 11(26)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.08 (br, 1H),7.61 (dd, J=8.0, 1.5 Hz, 1H), 7.37 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.01(ddd, J=8.0, 7.5, 1.0 Hz, 1H), 6.91 (dd, J=8.0, 1.0 Hz, 1H), 5.61 (s,1H), 2.53-2.43 (m, 1H), 1.94-1.85 (m, 2H), 1.82-1.45 (m, 16H).

EXAMPLE 11(27)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.61 (dd, J=8.0, 1.5 Hz, 1H), 7.37 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.01(ddd, J=8.0, 7.5, 1.0 Hz, 1H), 6.91 (dd, J=8.0, 1.0 Hz, 1H), 5.64 (s,1H), 2.31 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m, 4H), 1.71-1.67 (m,1H), 1.61 (s, 6H), 1.49-1.19 (m, 5H).

EXAMPLE 11(28)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.65 (br, 1H),7.95 (m, 2H), 7.51 (d, J=1.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.23 (m, 1H),6.86 (d, J=9.0 Hz, 1H), 6.31 (s, 1H), 2.37 (s, 3H), 1.66 (s, 6H).

EXAMPLE 11(29)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.62 (br, 1H),7.94 (m, 2H), 7.50-7.40 (m, 3H), 7.20 (d, J=3.0 Hz, 1H), 7.01 (dd,J=9.0, 3.0 Hz, 1H), 6.90 (d, J=9.0 Hz, 1H), 6.26 (s, 1H), 3.86 (s, 3H),1.65 (s, 6H).

EXAMPLE 11(30)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.56 (br, 1H),7.95 (m, 2H), 7.70 (d, J=2.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.36 (dd,J=8.5, 2.5 Hz, 1H), 6.91 (d, J=8.5 Hz, 1H), 6.28 (s, 1H), 1.66 (s, 6H).

EXAMPLE 11(31)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.55 (br, 1H),7.93 (m, 2H), 7.50-7.40 (m, 3H), 7.41 (dd, J=9.0, 3.0 Hz, 1H), 7.13(ddd, J=9.0, 8.0, 3.0 Hz, 1H), 6.92 (dd, J=9.0, 4.5 Hz, 1H), 6.25 (s,1H), 1.66 (s, 6H).

EXAMPLE 11(32)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.28 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.31 (br, 1H),7.22 (d, J=2.5 Hz, 1H), 7.08 (d, J=8.5 Hz, 1H), 6.94 (dd, J=8.5, 2.5 Hz,1H), 5.58 (s, 1H), 3.86 (s, 3H), 2.77 (s, 2H), 2.30 (m, 1H), 1.95-1.20(m, 10H), 1.28 (s, 6H).

EXAMPLE 11(33)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.29 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.23 (br, 1H),7.21 (d, J=2.5 Hz, 1H), 7.08 (d, J=8.5 Hz, 1H), 6.94 (dd, J=8.5, 2.5 Hz,1H), 5.55 (s, 1H), 3.86 (s, 3H), 2.77 (s, 2H), 2.46 (m, 1H), 2.00-1.40(m, 12H), 1.28 (s, 6H).

EXAMPLE 11(34)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.23 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.67 (br, 1H),7.67 (dd, J=7.5, 2.0 Hz, 1H), 7.36 (ddd, J=8.0, 7.5, 2.0 Hz, 1H), 7.26(d, J=2.5 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 7.05-6.90 (m, 3H), 6.22 (s,1H), 3.91 (s, 3H), 3.84 (s, 3H), 2.82 (s, 2H), 1.35 (s, 6H).

EXAMPLE 11(35)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.29 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.95 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 7.31 (d, J=2.5 Hz, 1H),7.16 (d, J=8.5 Hz, 1H), 7.02 (dd, J=8.5, 2.5 Hz, 1H), 6.21 (s, 1H), 3.88(s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 11(36)(Z)-2-(7-t-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.41 (br, 1H),7.69 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.10 (d, J=8.0 Hz,1H), 5.61 (s, 1H), 2.79 (s, 2H), 2.33 (m, 1H), 1.95-1.20 (m, 10H), 1.36(s, 9H), 1.29 (s, 6H).

EXAMPLE 11(37)(Z)-2-(7-t-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.33 (br, 1H),7.69 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.09 (d, J=8.0 Hz,1H), 5.58 (s, 1H), 2.79 (s, 2H), 2.49 (m, 1H), 2.00-1.40 (m, 12H), 1.36(s, 9H), 1.28 (s, 6H).

EXAMPLE 11(38)(Z)-2-(7-t-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.33 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.71 (br, 1H),7.77 (d, J=2.0 Hz, 1H), 7.72 (dd, J=7.5, 2.0 Hz, 1H), 7.44 (dd, J=8.0,2.0 Hz, 1H), 7.37 (ddd, J=8.0, 7.5, 2.0 Hz, 1H), 7.12 (d, J=8.0 Hz, 1H),7.02 (ddd, J=7.5, 7.5, 1.0 Hz, 1H), 6.98 (dd, J=8.0, 1.0 Hz, 1H), 6.34(s, 1H), 3.93 (s, 3H), 2.85 (s, 2H), 1.35 (s, 6H), 1.34 (s, 9H).

EXAMPLE 11(39)(Z)-2-(7-t-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.40 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 12.03 (br, 1H),8.01 (d, J=8.5 Hz, 2H), 7.78 (d, J=2.0 Hz, 1H), 7.74 (d, J=8.5 Hz, 2H),7.50 (d, J=8.0, 2.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 6.25 (s, 1H), 2.88(s, 2H), 1.38 (s, 9H), 1.38 (s, 6H).

EXAMPLE 11(40)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.89 (br, 1H),8.03-7.99 (m, 2H), 7.76-7.72 (m, 2H), 7.50 (dd, J=9.5, 2.5 Hz, 1H),7.22-7.14 (m, 2H), 6.19 (s, 1H), 2.89 (s, 2H), 1.38 (s, 6H).

EXAMPLE 11(41)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.89 (br, 1H),8.04-8.01 (m, 2H), 7.77-7.73 (m, 3H), 7.43 (dd, J=8.0, 2.0 Hz, 1H), 7.19(d, J=8.0 Hz, 1H), 6.21 (s, 1H), 2.89 (s, 2H), 1.38 (s, 6H).

EXAMPLE 11(42)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.61 (br, 1H),7.68 (dd, J=8.0, 2.0 Hz, 1H), 7.45-7.34 (m, 2H), 7.19-7.07 (m, 2H),7.04-6.96 (m, 2H), 6.22 (s, 1H), 3.92 (s, 3H), 2.85 (s, 2H), 1.35 (s,6H).

EXAMPLE 11(43)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.59 (br, 1H),7.70 (d, J=2.0 Hz, 1H), 7.66 (dd, J=8.0, 2.0 Hz, 1H), 7.40-7.34 (m, 2H),7.14 (d, J=8.0 Hz, 1H), 7.04-6.96 (m, 2H), 6.22 (s, 1H), 3.92 (s, 3H),2.85 (s, 2H), 1.35 (s, 6H).

EXAMPLE 11(44)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.39 (dd, J=10.0, 2.5 Hz, 1H), 7.16-7.05 (m, 2H), 5.56 (s, 1H), 2.80 (s,2H), 2.36-2.25 (m, 1H), 1.90-1.79 (m, 4H), 1.71-1.68 (m, 1H), 1.50-1.20(m, 1H).

EXAMPLE 11(45)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.39 (dd, J=9.5, 2.5 Hz, 1H), 7.16-7.05 (m, 2H), 5.52 (s, 1H), 2.80 (s,2H), 2.50-2.42 (m, 1H), 1.95-1.88 (m, 2H), 1.82-1.45 (m, 10H), 1.29 (s,6H).

EXAMPLE 11(46)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.23 (br, 1H),7.67 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.0, 2.0 Hz, 1H), 7.12 (d, J=8.0 Hz,1H), 5.58 (s, 10H), 2.80 (s, 2H), 2.31 (tt, J=11.5, 3.0 Hz, 1H),1.90-1.80 (m, 4H), 1.71-1.68 (m, 1H), 1.51-1.20 (m, 1H).

EXAMPLE 11(47)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.15 (br, 1H),7.67 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.0, 2.0 Hz, 1H), 7.11 (d, J=8.0 Hz,1H), 5.54 (s, 1H), 2.80 (s, 2H), 2.48 (tt, J=9.5, 4.0 Hz, 1H), 1.95-1.88(m, 2H), 1.82-1.47 (m, 10H), 1.28 (s, 6H).

EXAMPLE 11(48)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.30 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.32 (br, 1H),7.51 (s, 1H), 7.19 (m, 1H), 7.05 (d, J=8.0 Hz, 1H), 5.62 (s, 1H), 2.79(s, 2H), 2.38 (s, 3H), 2.30 (m, 1H), 1.95-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 11(49)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.23 (br, 1H),7.50 (s, 1H), 7.18 (m, 1H), 7.05 (d, J=7.5 Hz, 1H), 5.59 (s, 1H), 2.78(s, 2H), 2.46 (m, 1H), 2.38 (s, 3H), 2.00-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 11(50)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.67 (br, 1H),7.65 (dd, J=7.5, 2.0 Hz, 1H), 7.54 (s, 1H), 7.35 (ddd, J=8.0, 7.5, 2.0Hz, 1H), 7.20 (m, 1H), 7.07 (d, J=7.5 Hz, 1H), 7.00 (ddd, J=8.0, 8.0,1.0 Hz, 1H), 6.96 (dd, J=8.0, 1.0 Hz, 1H), 6.22 (s, 1H), 3.91 (s, 3H),2.84 (s, 2H), 2.37 (s, 3H), 1.34 (s, 6H).

EXAMPLE 11(51)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.40 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.96 (br, 1H),8.03 (d, J=8.5 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.60 (s, 1H), 7.27 (m,1H), 7.12 (d, J=7.5 Hz, 1H), 6.26 (s, 1H), 2.87 (s, 2H), 2.43 (s, 3H),1.37 (s, 6H).

EXAMPLE 11(52)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-nitrophenyl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.40 (br, 1H),7.85 (d, J=7.5 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.64-7.57 (m, 2H),7.52-7.41 (m, 2H), 7.33-7.27 (m, 1H), 7.21 (d, J=7.5 Hz, 1H), 5.86 (s,1H), 2.92 (s, 2H), 1.37 (s, 6H).

EXAMPLE 11(53)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-nitrophenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.94 (br, 1H),8.77 (dd, J=2.0, 2.0 Hz, 1H), 8.32-8.27 (m, 2H), 7.86 (dd, J=7.5, 1.0Hz, 1H), 7.62 (dd, J=8.0, 8.0 Hz, 1H), 7.48 (ddd, J=7.5, 7.5, 1.0 Hz,1H), 7.39 (ddd, J=7.5, 7.5, 1.0 Hz, 1H), 7.27-7.23 (m, 1H), 6.32 (s,1H), 2.94 (s, 2H), 1.39 (s, 6H).

EXAMPLE 11(54)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.00 (br, 1H),8.30-8.26 (m, 2H), 8.09-8.05 (m, 2H), 7.83 (dd, J=7.5, 1.0 Hz, 1H), 7.48(ddd, J=7.5, 7.5, 1.0 Hz, 1H), 7.37 (ddd, J=7.5, 7.5, 1.0 Hz, 1H),7.27-7.23 (m, 1H), 6.30 (s, 1H), 2.93 (s, 2H), 1.39 (s, 6H).

EXAMPLE 11(55)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,5-dimethoxyphenyl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.69 (br, 1H),7.75 (d, J=7.5 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H), 7.33-7.25 (m, 2H), 7.20(d, J=7.5 Hz, 1H), 6.92-6.91 (m, 2H), 6.37 (s, 1H), 3.88 (s, 3H), 3.81(s, 3H), 2.90 (s, 2H), 1.36 (s, 6H).

EXAMPLE 11(56)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,4-dimethoxyphenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.67 (br, 1H),7.78-7.75 (m, 2H), 7.39 (t, J=7.5 Hz, 1H), 7.33-7.25 (m, 1H), 7.19 (d,J=7.5 Hz, 1H), 6.55 (dd, J=8.5, 2.5 Hz, 1H), 6.50 (d, J=2.5 Hz, 1H),6.40 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 2.88 (s, 2H), 1.34 (s, 6H).

EXAMPLE 11(57)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

TLC: Rf0.22 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.78 (br, 1H),8.48 (m, 1H), 7.90-7.80 (m, 2H), 7.69 (dd, J=7.0, 1.0 Hz, 1H), 7.55-7.45(m, 3H), 7.22 (d, J=2.5 Hz, 1H), 7.14 (d, J=8.5 Hz, 1H), 6.98 (dd,J=8.0, 2.5 Hz, 1H), 6.04 (s, 1H), 3.80 (s, 3H), 2.88 (s, 2H), 1.40 (s,6H).

EXAMPLE 11(58)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(thiazol-2-yl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.63 (br, 1H),7.97-7.92 (m, 2H), 7.52 (d, J=3.0 Hz, 1H), 7.45 (dt, J=1.0, 7.5 Hz, 1H),7.35 (t, J=7.5 Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 6.80 (s, 1H), 2.92 (s,2H), 1.38 (s, 6H).

EXAMPLE 11(59)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyrrol-2-yl)ethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.14 (br, 1H),9.42 (br, 1H), 7.80 (dd, J=7.5, 1.0 Hz, 1H), 7.41 (dt, J=1.0, 7.5 Hz,1H), 7.33 (dt, J=1.0, 7.5 Hz, 1H), 7.20 (dd, J=7.5, 1.0 Hz, 1H), 6.94(m, 1H), 6.80 (m, 1H), 6.27 (m, 1H), 6.14 (s, 1H), 2.88 (s, 2H), 1.34(s, 6H).

EXAMPLE 11(60)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(antracen-9-yl)ethan1-one

TLC: Rf0.28 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.93 (br, 1H),8.44 (s, 1H), 8.26-8.22 (m, 2H), 8.03-7.98 (m, 2H), 7.59 (d, J=7.5 Hz,1H), 7.48-7.37 (m, 5H), 7.26-7.17 (m, 2H), 6.03 (s, 1H), 3.01 (s, 2H),1.49 (s, 6H).

EXAMPLE 11(61)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyrazin-2-yl)ethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.96 (br, 1H),9.35 (d, J=1.5 Hz, 1H), 8.63 (d, J=2.5 Hz, 1H), 8.59 (dd, J=2.5, 1.5 Hz,1H), 7.96 (d, J=7.5 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.36 (t, J=7.5 Hz,1H), 7.22 (d, J=7.5 Hz, 1H), 7.02 (s, 1H), 2.93 (s, 2H), 1.40 (s, 6H).

EXAMPLE 11(62)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.64 (dd, J=8.0, 1.5 Hz, 1H), 7.37 (ddd, J=8.0, 7.5, 1.5 Hz, 1H), 7.02(ddd, J=8.0, 7.5, 1.0 Hz, 1H), 6.91 (dd, J=8.0, 1.0 Hz, 1H), 5.80 (s,1H), 2.06 (br, 3H), 1.90-1.89 (m, 6H), 1.74 (br, 6H), 1.60 (s, 6H).

EXAMPLE 11(63)(Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.51 (s, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.05 (d, J=7.5 Hz, 1H), 5.76 (s,1H), 2.79 (s, 2H), 2.40 (s, 3H), 2.06 (br, 3H), 1.93 (br, 6H), 1.75 (br,6H), 1.28 (s, 6H).

EXAMPLE 11(64)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.47 (br, 1H),7.25 (d, J=2.5 Hz, 1H), 7.09 (d, J=8.0 Hz, 1H), 6.94 (dd, J=8.0, 2.5 Hz,1H), 5.73 (s, 1H), 3.87 (s, 3H), 2.77 (s, 2H), 2.05 (br, 3H), 1.91 (br,6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 11(65)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(thiophen-3-yl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.67 (br, 1H),7.93 (dd, J=3.0, 1.0 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.56 (dd, J=5.0,1.0 Hz, 1H), 7.43 (t, J=7.5 Hz, 1H), 7.37-7.29 (m, 2H), 7.21 (d, J=7.5Hz, 1H), 6.18 (s, 1H), 2.89 (s, 2H), 1.35 (s, 6H).

EXAMPLE 11(66)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(5-methylfuran-2-yl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.54 (br, 1H),7.84 (dd, J=7.5, 1.0 Hz, 1H), 7.42 (dt, J=1.0, 7.5 Hz, 1H), 7.34 (dt,J=1.0, 7.5 Hz, 1H), 7.20 (dd, J=7.5, 1.0 Hz, 1H), 6.95 (d, J=3.5 Hz,1H), 6.23 (s, 1H), 6.10 (d, J=3.5 Hz, 1H), 2.88 (s, 2H), 2.39 (s, 3H),1.34 (s, 6H).

EXAMPLE 11(67)(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.61 (hexane ethyl acetate=3:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.32 (dd, J=9.5, 3.0 Hz, 1H), 7.09 (ddd, J=9.5, 9.0, 3.0 Hz, 1H), 6.88(dd, J=9.0, 4.5 Hz, 1H), 5.72 (s, 1H), 2.07 (br, 3H), 1.89 (br, 6H),1.75 (br, 6H), 1.59 (s, 6H).

EXAMPLE 11(68)(Z)-2-(7-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.58 (d, J=2.5 Hz, 1H), 7.32 (dd, J=9.0, 2.5 Hz, 1H), 6.87 (d, J=9.0 Hz,1H), 5.74 (s, 1H), 2.07 (br, 3H), 1.89 (br, 6H), 1.75 (br, 6H), 1.59 (s,6H).

EXAMPLE 11(69)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.32 (br, 1H),7.11 (d, J=3.0 Hz, 1H), 6.97 (dd, J=9.0, 3.0 Hz, 1H), 6.85 (d, J=9.0 Hz,1H), 5.73 (s, 1H), 3.84 (s, 3H), 2.06 (br, 3H), 1.89 (br, 6H), 1.74 (br,6H), 1.58 (s, 6H).

EXAMPLE 11(70)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

TLC: Rf0.20 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.70 (br, 1H),8.46 (m, 1H), 7.90-7.85 (m, 2H), 7.83 (d, J=2.0 Hz, 1H), 7.70 (dd,J=7.0, 1.5 Hz, 1H), 7.55-7.45 (m, 4H), 7.11 (d, J=8.0 Hz, 1H), 6.03 (s,1H), 2.89 (s, 2H), 1.41 (s, 6H).

EXAMPLE 11(71)(Z)-2-(3,3,7-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.40 (d, J=2.0 Hz, 1H), 7.18 (dd, J=8.5, 2.0 Hz, 1H), 6.81 (d, J=8.5 Hz,1H), 5.77 (s, 1H), 2.35 (s, 3H), 2.07 (br, 3H), 1.90 (br, 6H), 1.75 (br,6H), 1.58 (s, 6H).

EXAMPLE 11(72)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.90 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.76-7.71 (m, 3H), 7.34 (dd, J=8.5, 2.5 Hz, 1H),7.24 (d, J=2.5 Hz, 1H), 6.22 (s, 1H), 2.90 (s, 2H), 1.38 (s, 6H).

EXAMPLE 11(73)(Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.18 (br, 1H),7.99 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 7.45 (d, J=7.5 Hz, 1H),7.33 (t, J=7.5 Hz, 1H), 7.15 (d, J=7.5 Hz, 1H), 6.81 (s, 1H), 2.87 (s,2H), 1.34 (s, 6H).

EXAMPLE 11(74)(Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.49 (br, 1H),7.37 (dd, J=8.0, 1.0 Hz, 1H), 7.24 (t, J=8.0 Hz, 1H), 7.08 (dd, J=8.0,1.0 Hz, 1H), 6.11 (s, 1H), 2.79 (s, 2H), 2.27 (tt, J=11.5, 3.5 Hz, 1H),1.91-1.87 (m, 2H), 1.82-1.78 (m, 2H), 1.67 (m, 1H), 1.53-1.25 (m, 1H).

EXAMPLE 11(75)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(5-methylthiophen-2-yl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.40 (br, 1H),7.79 (dd, J=7.5, 1.5 Hz, 1H), 7.46-7.39 (m, 2H), 7.33 (dt, J=1.5, 7.5Hz, 1H), 7.20 (dd, J=7.5, 1.5 Hz, 1H), 6.76 (dq, J=4.0, 1.0 Hz, 1H),6.15 (s, 1H), 2.88 (s, 2H), 2.53 (d, J=1.0 Hz, 3H), 1.33 (s, 6H).

EXAMPLE 11(76)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,5-dimethylfuran-3-yl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.50 (br, 1H),7.74 (dd, J=7.5, 1.5 Hz, 1H), 7.40 (dt, J=1.5, 7.5 Hz, 1H), 7.31 (dt,J=1.5, 7.5 Hz, 1H), 7.19 (dd, J=7.5, 1.5 Hz, 1H), 6.23 (d, J=1.0 Hz,1H), 5.92 (s, 1H), 2.87 (s, 2H), 2.61 (s, 3H), 2.26 (d, J=1.0 Hz, 3H),1.33 (s, 6H).

EXAMPLE 11(77)(Z)-2-(6-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.21 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.69 (br, 1H),7.99 (d, J=9.0 Hz, 2H), 7.74 (d, J=9.0 Hz, 2H), 7.65 (d, J=8.5 Hz, 1H),7.07 (dd, J=8.5, 2.0 Hz, 1H), 7.01 (d, J=2.0 Hz, 1H), 6.22 (s, 1H), 1.68(s, 6H).

EXAMPLE 11(78)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.41 (br, 1H),7.41 (dd, J=10.0, 2.5 Hz, 1H), 7.17-7.05 (m, 2H), 5.71 (s, 1H), 2.80 (s,2H), 2.06 (br, 3H), 1.91 (br, 6H), 1.75 (br, 6H), 1.29 (s, 6H).

EXAMPLE 11(79)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.42 (br, 1H),7.67 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.0, 2.0 Hz, 1H), 7.12 (d, J=8.0 Hz,1H), 5.72 (s, 1H), 2.80 (s, 2H), 2.07 (br, 3H), 1.91 (br, 6H), 1.75 (br,6H), 1.29 (s, 6H).

EXAMPLE 11(80)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.43 (br, 1H),7.65 (d, J=8.0 Hz, 1H), 7.27 (dd, J=8.0, 2.0 Hz, 1H), 7.17 (d, J=2.0 Hz,1H), 5.74 (s, 1H), 2.81 (s, 2H), 2.05 (br, 3H), 1.90 (br, 6H), 1.74 (br,6H), 1.29 (s, 6H).

EXAMPLE 11(81)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-bromophenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.84 (br, 1H),7.84-7.80 (m, 3H), 7.56 (d, J=8.5 Hz, 2H), 7.44 (t, J=7.5 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 6.27 (s, 1H), 2.91 (s, 2H),1.37 (s, 6H).

EXAMPLE 11(82)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(5-cyanothiophen-2-yl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.63 (br, 1H),7.78 (d, J=7.5 Hz, 1H), 7.58 (d, J=4.0 Hz, 1H), 7.53 (d, J=4.0 Hz, 1H),7.48 (t, J=7.5 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 1H),6.15 (s, 1H), 2.92 (s, 2H), 1.36 (s, 6H).

EXAMPLE 11(83)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylthiophenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.81 (br, 1H),7.89 (d, J=8.5 Hz, 2H), 7.83 (d, J=7.5 Hz, 1H), 7.43 (t, J=7.5 Hz, 1H),7.34 (t, J=7.5 Hz, 1H), 7.28 (d, J=8.5 Hz, 2H), 7.21 (d, J=7.5 Hz, 1H),6.31 (s, 1H), 2.90 (s, 2H), 2.53 (s, 3H), 1.36 (s, 6H).

EXAMPLE 11(84)(Z)-2-(6-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.59 (br, 1H),7.93 (m, 2H), 7.66 (d, J=8.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.04 (dd,J=8.5, 2.0 Hz, 1H), 6.98 (d, J=2.0 Hz, 1H), 6.29 (s, 1H), 1.66 (s, 6H).

EXAMPLE 11(85)(Z)-2-(6-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.44 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.11 (br, 1H),7.53 (d, J=8.5 Hz, 1H), 6.98 (dd, J=8.5, 2.0 Hz, 1H), 6.94 (d, J=2.0 Hz,1H), 5.60 (s, 1H), 2.30 (m, 1H), 1.90-1.20 (m, 10H), 1.66 (s, 6H).

EXAMPLE 11(86)(Z)-2-(6-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.60 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.02 (br, 1H),7.53 (d, J=8.5 Hz, 1H), 6.98 (dd, J=8.5, 2.0 Hz, 1H), 6.93 (d, J=2.0 Hz,1H), 5.56 (s, 1H), 2.47 (m, 1H), 1.95-1.40 (m, 12H), 1.59 (s, 6H).

EXAMPLE 11(87)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-dimethylaminophenyl)ethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.65 (br, 1H),7.91 (d, J=9.0 Hz, 2H), 7.83 (d, J=7.5 Hz, 1H), 7.40 (t, J=7.5 Hz, 1H),7.33 (t, J=7.5 Hz, 1H), 7.19 (d, J=7.5 Hz, 1H), 6.71 (d, J=9.0 Hz, 2H),6.32 (s, 1H), 3.04 (s, 6H), 2.88 (s, 2H), 1.34 (s, 6H).

EXAMPLE 11(88)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-mesylphenyl)ethan-1-one

TLC: Rf0.32 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.97 (br, 1H),8.10 (d, J=9.0 Hz, 2H), 8.00 (d, J=9.0 Hz, 2H), 7.83 (d, J=7.5 Hz, 1H),7.47 (t, J=7.5 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 1H),6.30 (s, 1H), 3.09 (s, 3H), 2.93 (s, 2H), 1.39 (s, 6H).

EXAMPLE 11(89)(Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.03 (br, 1H),7.95-7.91 (m, 2H), 7.44-7.41 (m, 4H), 7.29 (m, 1H), 7.13 (dd, J=7.5, 1.5Hz, 1H), 6.85 (s, 1H), 2.86 (s, 2H), 1.33 (s, 6H).

EXAMPLE 11(90)(Z)-2-(6-chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (ethyl acetate:hexane=1:10); NMR (CDCl₃): δ 11.28 (br, 1H),7.56 (d, J=8.5 Hz, 1H), 6.99 (dd, J=8.5, 2.0 Hz, 1H), 6.93 (d, J=2.0 Hz,1H), 5.76 (s, 1H), 2.06 (m, 3H), 1.88 (m, 6H), 1.74 (m, 6H), 1.59 (s,6H).

EXAMPLE 11(91)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.27 (br, 1H),7.63 (d, J=8.5 Hz, 1H), 7.27 (dd, J=8.5, 2.0 Hz, 1H), 7.19 (d, J=2.0 Hz,1H), 5.59 (s, 1H), 4.05 (m, 2H), 3.45 (dt, J=3.0, 11.5 Hz, 2H), 2.82 (s,2H), 2.51 (m, 1H), 1.90-1.70 (m, 4H), 1.30 (s, 6H).

EXAMPLE 11(92)(Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.39 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.66 (d, J=2.0 Hz, 1H), 7.37 (dd, J=8.0, 2.0 Hz, 1H), 7.13 (d, J=8.0 Hz,1H), 5.58 (s, 1H), 4.05 (m, 2H), 3.46 (dt, J=3.0, 11.5 Hz, 2H), 2.81 (s,2H), 2.54 (m, 1H), 1.90-1.70 (m, 4H), 1.30 (s, 6H).

EXAMPLE 11(93)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.38 (dd, J=9.5, 2.5 Hz, 1H), 7.20-7.05 (m, 2H), 5.56 (s, 1H), 4.05 (m,2H), 3.46 (dt, J=3.0, 11.5 Hz, 2H), 2.82 (s, 2H), 2.53 (m, 1H),1.90-1.70 (m, 4H), 1.30 (s, 6H).

EXAMPLE 11(94)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,4-dichlorophenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.56 (br, 1H),7.71 (d, J=7.5 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.46-7.41 (m, 2H),7.34-7.26 (m, 2H), 7.21 (d, J=7.5 Hz, 1H), 5.94 (s, 1H), 2.92 (s, 2H),1.38 (s, 6H).

EXAMPLE 11(95)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2,5-dichlorothiophen-3-yl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.61 (br, 1H),7.76 (d, J=7.5 Hz, 1H), 7.44 (t, J=7.5 Hz, 1H), 7.34 (t, J=7.5 Hz, 1H),7.21 (d, J=7.5 Hz, 1H), 7.16 (s, 1H), 6.17 (s, 1H), 2.90 (s, 2H), 1.36(s, 6H).

EXAMPLE 11(96)(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.48 (br, 1H),7.72 (dd, J=8.5, 5.5 Hz, 1H), 6.99 (ddd, J=8.5, 8.5, 2.5 Hz, 1H), 6.88(dd, J=8.5, 2.5 Hz, 1H), 5.72 (s, 1H), 2.82 (s, 2H), 2.05 (m, 3H), 1.91(m, 6H), 1.74 (m, 6H), 1.30 (s, 6H).

EXAMPLE 11(97)(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.13 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.94 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.82 (dd, J=8.5, 5.5 Hz, 1H), 7.72 (d, J=8.5 Hz,2H), 7.05 (ddd, J=8.5, 8.5, 2.5 Hz, 1H), 6.95 (dd, J=8.5, 2.5 Hz, 1H),6.21 (s, 1H), 2.91 (s, 2H), 1.38 (s, 6H).

EXAMPLE 11(98)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylnaphthalen-1-yl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.76 (br, 1H),8.54 (m, 1H), 8.03 (m, 1H), 7.71 (d, J=7.5 Hz, 1H), 7.61 (d, J=7.0 Hz,1H), 7.56-7.50 (m, 2H), 7.41 (t, J=7.5 Hz, 1H), 7.35-7.25 (m, 2H), 7.22(d, J=7.5 Hz, 1H), 6.08 (s, 1H), 2.94 (s, 2H), 2.73 (s, 3H), 1.41 (s,6H).

EXAMPLE 11(99)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-fluoronaphthalen-1-yl)ethan-1-one

TLC: Rf0.46 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.76 (br, 1H),8.55 (m, 1H), 8.14 (m, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.67 (dd, J=8.0, 5.5Hz, 1H), 7.60-7.53 (m, 2H), 7.43 (t, J=7.5 Hz, 1H), 7.29 (t, J=7.5 Hz,1H), 7.23 (d, J=7.5 Hz, 1H), 7.14 (dd, J=10.5, 8.0 Hz, 1H), 6.06 (s,1H), 2.95 (s, 2H), 1.41 (s, 6H).

EXAMPLE 11(100)(Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (brs, 1H),8.69 (d, J=2.4 Hz, 1H), 8.29 (dd, J=8.4, 2.4 Hz, 1H), 8.00-7.95 (m, 2H),7.52-7.44 (m, 3H), 7.42 (d, J=8.4 Hz, 1H), 6.40 (s, 1H), 3.01 (s, 2H),1.39 (s, 6H).

EXAMPLE 11(101)(Z)-2-(spiro[6-chloro-3,4-dihydro-(2H)-isoquinolin-3,4′-3,4,5,6-tetrahydropyran]-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.43 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 12.35 (br, 1H),7.94 (m, 2H), 8.76 (d, J=8.5 Hz, 1H), 7.50-7.40 (m, 3H), 7.32 (dd,J=8.5, 2.0 Hz, 1H), 7.25 (d, J=2.0 Hz, 1H), 6.34 (s, 1H), 3.86 (m, 4H),2.93 (s, 2H), 1.74 (m, 4H).

EXAMPLE 11(102)(Z)-2-(spiro[6-chloro-3,4-dihydro-(2H)-isoquinolin-3,4′-3,4,5,6-tetrahydropyran]-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 12.48 (br, 1H),8.02 (d, J=8.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 1H),7.34 (dd, J=8.5, 2.0 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 6.28 (s, 1H), 3.86(m, 4H), 2.95 (s, 2H), 1.76 (m, 4H).

EXAMPLE 11(103)(Z)-2-(spiro[6-chloro-3,4-dihydro-(2H)-isoquinolin-3,4′-3,4,5,6-tetrahydropyran]-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.56 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.92 (br, 1H),7.64 (d, J=8.5 Hz, 1H), 7.28 (dd, J=8.5, 2.0 Hz, 1H), 7.20 (d, J=2.0 Hz,1H), 5.79 (s, 1H), 3.80 (m, 4H), 2.86 (s, 2H), 2.06 (m, 3H), 1.91 (m,6H), 1.80-1.60 (m, 10H).

EXAMPLE 11(104)(Z)-2-(3,3-dimethyl-3′,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(noradamantan-1-yl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.70 (dd, J=7.5, 1.0 Hz, 1H), 7.38 (dt, J=1.0, 7.5 Hz, 1H), 7.29 (dt,J=1.0, 7.5 Hz, 1H), 7.17 (dd, J=7.5, 1.0 Hz, 1H), 5.74 (s, 1H), 2.85 (s,2H), 2.72 (t, J=6.5 Hz, 1H), 2.32 (br, 2H), 2.12-2.07 (m, 2H), 1.89-1.81(m, 4H), 1.67-1.63 (m, 4H), 1.30 (s, 6H).

EXAMPLE 11(105)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(noradamantan-1-yl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.30 (br, 1H),7.63 (d, J=8.5 Hz, 1H), 7.26 (dd, J=8.5, 2.0 Hz, 1H), 7.18 (d, J=2.0 Hz,1H), 5.69 (s, 1H), 2.82 (s, 2H), 2.71 (t, J=6.5 Hz, 1H), 2.32 (br, 2H),2.10-2.05 (m, 2H), 1.88-1.80 (m, 4H), 1.69-1.63 (m, 4H), 1.30 (s, 6H).

EXAMPLE 11(106)(Z)-2-(6-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.75 (br, 1H),7.99 (d, J=8.5 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.63 (d, J=9.0 Hz, 1H),6.64 (dd, J=9.0, 2.5 Hz, 1H), 6.48 (d, J=2.5 Hz, 1H), 6.17 (s, 1H), 3.85(s, 3H), 1.69 (s, 6H).

EXAMPLE 11(107)(Z)-2-(6-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.66 (br, 1H),7.95-7.92 (m, 2H), 7.65 (d, J=8.5 Hz, 1H), 7.49-7.40 (m, 3H), 6.63 (dd,J=8.5, 2.5 Hz, 1H), 6.46 (d, J=2.5 Hz, 1H), 6.24 (s, 1H), 3.84 (s, 3H),1.67 (s, 6H).

EXAMPLE 11(108)(Z)-2-(6-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.37 (br, 1H),7.55 (d, J=9.0 Hz, 1H), 6.58 (dd, J=9.0, 2.5 Hz, 1H), 6.42 (d, J=2.5 Hz,1H), 5.70 (s, 1H), 3.82 (s, 3H), 2.05 (br, 3H), 1.89 (br, 6H), 1.74 (br,6H), 1.60 (s, 6H).

EXAMPLE 11(109)(Z)-2-(3,3,6-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.51 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.63 (br, 1H),7.94 (m, 2H), 7.62 (d, J=8.0 Hz, 1H), 7.50-7.40 (m, 3H), 6.87 (m, 1H),6.77 (s, 1H), 6.30 (s, 1H), 2.37 (s, 3H), 1.66 (s, 6H).

EXAMPLE 11(110)(Z)-2-(3,3,6-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.39 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.73 (br, 1H),8.00 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz, 2H), 7.59 (d, J=8.0 Hz, 1H),6.89 (m, 1H), 6.79 (s, 1H), 6.23 (s, 1H), 2.38 (s, 3H), 1.67 (s, 6H).

EXAMPLE 11(111)(Z)-2-(3,3,6-trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.70 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.34 (br, 1H),7.51 (d, J=8.0 Hz, 1H), 6.82 (m, 1H), 6.73 (s, 1H), 5.76 (s, 1H), 2.35(s, 3H), 2.05 (m, 3H), 1.90 (m, 6H), 1.74 (m, 6H), 1.59 (s, 6H).

EXAMPLE 11(112)(Z)-2-(3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.17 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.17 (br, 1H),7.60 (dd, J=8.0, 1.5 Hz, 1H), 7.39 (ddd, J=8.0, 8.0, 1.5 Hz, 1H), 7.02(ddd, J=8.0, 8.0, 1.0 Hz, 1H), 6.92 (dd, J=8.0, 1.0 Hz, 1H), 5.64 (s,1H), 4.05 (m, 2H), 3.46 (m, 2H), 2.54 (m, 1H), 1.90-1.70 (m, 4H), 1.61(s, 6H).

EXAMPLE 11(113)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-chloro-4-mesylphenyl)ethan-1-one

TLC: Rf0.09 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.58 (br, 1H),8.00 (d, J=1.5 Hz, 1H), 7.86 (dd, J=8.0, 1.5 Hz, 1H), 7.72-7.70 (m, 2H),7.46 (t, J=7.5 Hz, 1H), 7.32 (t, J=7.5 Hz, 1H), 7.23 (d, J=7.5 Hz, 1H),5.89 (s, 1H), 3.09 (s, 3H), 2.94 (s, 2H), 1.40 (s, 6H).

EXAMPLE 11(114)(Z)-2-(6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-phenylethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.08 (br, 1H),7.94-7.91 (m, 2H), 7.46-7.40 (m, 3H), 7.32 (d, J=5.0 Hz, 1H), 7.17 (d,J=5.0 Hz, 1H), 6.14 (s, 1H), 3.00 (s, 2H), 1.43 (s, 6H).

EXAMPLE 11(115)(Z)-2-(6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 10.74 (br, 1H),7.23 (d, J=5.5 Hz, 1H), 7.12 (d, J=5.5 Hz, 1H), 5.59 (s, 1H), 2.93 (s,2H), 2.05 (br, 3H), 1.89 (br, 6H), 1.73 (br, 6H), 1.36 (s, 6H).

EXAMPLE 11(116)(Z)-2-(6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.21 (br, 1H),7.99 (d, J=8.0 Hz, 2H), 7.72 (d, J=8.0 Hz, 2H), 7.31 (d, J=5.0 Hz, 1H),7.20 (d, J=5.0 Hz, 1H), 6.07 (s, 1H), 3.02 (s, 2H), 1.45 (s, 6H).

EXAMPLE 11(117)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.67 (d, J=8.5 Hz, 1H), 6.81 (dd, J=8.5, 2.5 Hz, 1H), 6.68 (d, J=2.5 Hz,1H), 5.70 (s, 1H), 3.85 (s, 3H), 2.80 (s, 2H), 2.05 (br, 3H), 1.91 (br,6H), 1.74 (br, 6H), 1.29 (s, 6H).

EXAMPLE 11(118)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.18 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.96 (br, 1H),8.01 (d, J=8.5 Hz, 2H), 7.77-7.70 (m, 3H), 6.87 (dd, J=8.5, 2.5 Hz, 1H),6.74 (d, J=2.5 Hz, 1H), 6.20 (s, 1H), 3.88 (s, 3H), 2.88 (s, 2H), 1.38(s, 6H).

EXAMPLE 11(119)(Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.39 (br, 1H),7.91 (s, 1H), 7.28 (s, 1H), 5.69 (s, 1H), 2.76 (s, 2H), 2.07 (m, 3H),1.91 (m, 6H), 1.75 (m, 6H), 1.29 (s, 6H).

EXAMPLE 11(120)(Z)-2-(2-chloro-6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-phenylethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 10.96 (br, 1H),7.92-7.89 (m, 2H), 7.46-7.40 (m, 3H), 7.14 (s, 1H), 6.02 (s, 1H), 2.90(s, 2H), 1.43 (s, 6H).

EXAMPLE 11(121)(Z)-2-(2-chloro-6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 10.62 (br, 1H),7.05 (s, 1H), 5.47 (s, 1H), 2.82 (s, 2H), 2.05 (br, 3H), 1.87 (br, 6H),1.73 (br, 6H), 1.36 (s, 6H).

EXAMPLE 11(122)(Z)-2-(2-chloro-6,6-dimethyl-4,5,6,7-tetrahydrothiopheno[3,2-c]pyridin-4-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.09 (br, 1H),7.97 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 7.13 (s, 1H), 5.95 (s,1H), 2.92 (s, 2H), 1.45 (s, 6H).

EXAMPLE 11(123)(Z)-2-(5-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.84 (brs, 1H),7.97-7.91 (m, 2H), 7.48-7.40 (m, 4H), 7.30 (t, J=8.1 Hz, 1H), 7.00 (d,J=8.1 Hz, 1H), 6.33 (s, 1H), 3.87 (s, 3H), 2.90 (s, 2H), 1.37 (s, 6H).

EXAMPLE 11(124)(Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.48 (brs, 1H),7.61 (d, J=8.1 Hz, 1H), 7.09 (brd, J=8.1 Hz, 1H), 6.97 (brs, 1H), 5.75(s, 1H), 2.79 (s, 2H), 2.37 (s, 3H), 2.05 (brs, 3H), 1.91 (d, J=3.0 Hz,6H), 1.74 (d, J=3.0 Hz, 6H), 1.29 (s, 6H).

EXAMPLE 11(125)(Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.94 (brs, 1H),8.01 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.70 (d, J=8.4 Hz, 1H),7.16 (brd, J=8.4 Hz, 1H), 7.04 (brs, 1H), 6.25 (s, 1H), 2.87 (s, 2H),2.41 (s, 3H), 1.37 (s, 6H).

EXAMPLE 11(126)(Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.14 (ethyl acetate:hexane=1:1); NMR (CDCl₃).: δ 11.91 (br, 1H),8.67 (d, J=2.0 Hz, 1H), 8.32 (dd, J=8.0, 2.0 Hz, 1H), 8.05 (d, J=8.5 Hz,2H), 7.77 (d, J=8.5 Hz, 2H), 7.45 (d, J=8.0 Hz, 1H), 6.34 (s, 1H), 6.04(s, 2H), 1.41 (s, 6H).

EXAMPLE 11(127)(Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.29 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.15 (br, 1H),8.23 (s, 1H), 7.38 (s, 1H), 5.61 (s, 1H), 2.88 (s, 2H), 2.33 (m, 1H),1.90-1.65 (m, 5H), 1.55-1.20 (m, 5H), 1.31 (s, 6H).

EXAMPLE 11(128)(Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.30 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.08 (br, 1H),8.23 (s, 1H), 7.39 (s, 1H), 5.58 (s, 1H), 2.88 (s, 2H), 2.51 (m, 1H),1.95-1.20 (m, 12H), 1.31 (s, 6H).

EXAMPLE 11(129)(Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.13 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.83 (br, 1H),8.34 (s, 1H), 8.01 (d, J=8.5 Hz, 2H), 7.76 (d, J=8.5 Hz, 2H), 7.46 (s,1H), 6.24 (s, 1H), 2.97 (s, 2H), 1.41 (s, 6H).

EXAMPLE 11(130)(Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.36 (br, 1H),8.22 (s, 1H), 7.39 (s, 1H), 5.75 (s, 1H), 2.88 (s, 2H), 2.07 (m, 3H),1.90 (m, 6H), 1.75 (m, 6H), 1.32 (s, 6H).

EXAMPLE 11(131)(Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.41 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 12.01(br, 1H), 8.03 (d, J=8.0 Hz, 2H), 7.74 (s, 1H), 7.73 (d, J=8.0 Hz, 2H),7.41 (d, J=7.5 Hz, 1H), 7.19 (d, J=7.5 Hz, 1H), 6.29 (s, 1H), 3.48 (s,2H), 2.90 (s, 2H), 2.28 (s, 6H), 1.37 (s, 6H).

EXAMPLE 11(132)(Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.39 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.55(br, 1H), 7.66 (s, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.15 (d, J=7.5 Hz, 1H),5.80 (s, 1H), 3.55 (br, 2H), 2.82 (s, 2H), 2.33 (s, 6H), 2.06 (m, 3H),1.92 (m, 6H), 1.75 (m, 6H), 1.29 (s, 6H).

EXAMPLE 11(133)(Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.91 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.71 (d, J=8.5 Hz, 2H), 7.13 (s, 1H), 6.59 (s,1H), 6.12 (s, 1H), 3.92 (s, 3H), 3.88 (br, 2H), 2.80 (s, 2H), 1.37 (s,6H).

EXAMPLE 11(134)(Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.46 (br, 1H),7.07 (s, 1H), 6.54 (s, 1H), 5.62 (s, 1H), 3.89 (s, 3H), 3.82 (br, 2H),2.72 (s, 2H), 2.05 (br, 3H), 1.91 (br, 6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 11(135)(Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1′-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.32 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.33 (br, 1H),7.36 (s, 1H), 7.17 (s, 1H), 5.54 (s, 1H), 2.86 (s, 6H), 2.74 (s, 2H),2.32 (m, 1H), 1.95-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 11(136)(Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.25 (br, 1H),7.35 (s, 1H), 7.17 (s, 1H), 5.51 (s, 1H), 2.86 (s, 6H), 2.74 (s, 2H),2.48 (m, 1H), 1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 11(137)(Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.95 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.43 (s, 1H), 7.24 (s,1H), 6.17 (s, 1H), 2.89 (s, 6H), 2.82 (s, 2H), 1.37 (s, 6H).

EXAMPLE 11(138)(Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.51 (br, 1H),7.36 (s, 1H), 7.16 (s, 1H), 5.69 (s, 1H), 2.86 (s, 6H), 2.73 (s, 2H),2.06 (m, 3H), 1.91 (m, 6H), 1.74 (m, 6H), 1.28 (s, 6H).

EXAMPLE 11(139)(Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.16 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.98 (brs, 1H),8.01 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.40 (s, 1H), 7.01 (s,1H), 6.19 (s, 1H), 2.81 (s, 2H), 2.76 (s, 6H), 2.37 (s, 3H), 1.37 (s,6H).

EXAMPLE 11(140)(Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.55 (brs, 1H),7.33 (s, 1H), 6.95 (s, 1H), 5.71 (s, 1H), 2.74 (s, 6H), 2.73 (s, 2H),2.34 (s, 3H), 2.09-2.03 (m, 3H), 1.94-1.90 (m, 6H), 1.77-1.73 (m, 6H),1.28 (s, 6H).

EXAMPLE 11(141)(Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.36 (brs, 1H),7.32 (s, 1H), 6.95 (s, 1H), 5.56 (s, 1H), 2.74 (s, 8H), 2.34 (s, 3H),2.31 (m, 1H), 1.92-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 11(142)(Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.29 (brs, 1H),7.32 (s, 1H), 6.94 (s, 1H), 5.52 (s, 1H), 2.74 (s, 6H), 2.73 (s, 2H),2.47 (m, 1H), 2.34 (s, 3H), 1.97-1.43 (m, 12H), 1.27 (s, 6H).

EXAMPLE 11(143)(Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.44 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.34(br, 1H), 7.63 (d, J=1.5 Hz, 1H), 7.34 (dd, J=8.0, 1.5 Hz, 1H), 7.12 (d,J=8.0 Hz, 1H), 5.66 (s, 1H), 3.46 (s, 2H), 2.82 (s, 2H), 2.32 (m, 1H),2.28 (s, 6H), 1.90-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 11(144)(Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.46 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.27(br, 1H), 7.63 (s, 1H), 7.33 (d, J=7.5 Hz, 1H), 7.12 (d, J=7.5 Hz, 1H),5.62 (s, 1H), 3.45 (s, 2H), 2.82 (s, 2H), 2.48 (m, 1H), 2.27 (s, 6H),1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 11(145)(Z)-2-(6-methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.97 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 6.89 (s, 1H), 6.56 (s,1H), 6.17 (s, 1H), 4.33 (br, 1H), 3.92 (s, 3H), 2.95 (s, 3H), 2.81 (s,2H), 1.37 (s, 6H).

EXAMPLE 11(146)(Z)-2-(6-methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.57 (br, 1H),6.85 (s, 1H), 6.50 (s, 1H), 5.68 (s, 1H), 4.23 (br, 1H), 3.88 (s, 3H),2.94 (s, 3H), 2.72 (s, 2H), 2.05 (br, 3H), 1.92 (br, 6H), 1.74 (br, 6H),1.29 (s, 6H).

EXAMPLE 11(147)(Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.37 (br, 1H),7.23 (s, 1H), 6.60 (s, 1H), 5.51 (s, 1H), 3.93 (s, 3H), 2.82 (s, 6H),2.76 (s, 2H), 2.30 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m, 4H), 1.69 (m,1H), 1.56-1.20 (m, 1H).

EXAMPLE 11(148)(Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.30 (br, 1H),7.23 (s, 1H), 6.60 (s, 1H), 5.48 (s, 1H), 3.93 (s, 3H), 2.82 (s, 6H),2.76 (s, 2H), 2.46 (m, 1H), 1.95-1.88 (m, 2H), 1.83-1.45 (m, 10H), 1.29(s, 6H).

EXAMPLE 11(149)(Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.14 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 12.02 (brs, 1H),8.00 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 7.09 (d, J=8.7 Hz, 1H),7.08 (d, J=2.4 Hz, 1H), 6.86 (dd, J=8.7, 2.4 Hz, 1H), 6.21 (s, 1H), 3.02(s, 6H), 2.81 (s, 2H), 1.36 (s, 6H).

EXAMPLE 11(150)(Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.57 (brs, 1H),7.05 (d, J=2.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 6.80 (dd, J=8.4, 2.4 Hz,1H), 5.73 (s, 1H), 2.99 (s, 6H), 2.73 (s, 2H), 2.08-2.02 (m, 3H),1.94-1.90 (m, 6H), 1.76-1.72 (m, 6H), 1.28 (s, 6H).

EXAMPLE 11(151)(Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.28 (br, 1H),7.05 (s, 1H), 6.54 (s, 1H), 5.48 (s, 1H), 3.89 (s, 3H), 3.80 (br, 2H),2.72 (s, 2H), 2.26 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m, 4H), 1.68 (m,1H), 1.56-1.22 (m, 1H).

EXAMPLE 11(152)(Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.19 (br, 1H),7.05 (s, 1H), 6.53 (s, 1H), 5.44 (s, 1H), 3.89 (s, 3H), 3.80 (br, 2H),2.72 (s, 2H), 2.42 (m, 1H), 1.95-1.87 (m, 2H), 1.82-1.46 (m, 10H), 1.28(s, 6H).

EXAMPLE 11(153)(Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.25 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.19 (br, 1H),7.91 (s, 1H), 7.28 (s, 1H), 5.54 (s, 1H), 2.76 (s, 2H), 2.31 (m, 1H),1.90-1.20 (m, 10H), 1.29 (s, 6H).

EXAMPLE 11(154)(Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.11 (br, 1H),7.91 (s, 1H), 7.28 (s, 1H), 5.51 (s, 1H), 2.76 (s, 2H), 2.48 (m, 1H),1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 11(155)(Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.67 (ethyl acetate:hexane=2:3); NMR (CDCl₃): δ 11.23 (br, 1H),8.56 (d, J=2.5 Hz, 1H), 8.24 (dd, J=8.0, 2.5 Hz, 1H), 7.37 (d, J=8.0 Hz,1H), 5.71 (s, 1H), 2.95 (s, 2H), 2.37 (m, 1H), 1.95-1.20 (m, 10H), 1.31(s, 6H).

EXAMPLE 11(156)(Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.45 (br, 1H),7.86 (s, 1H), 6.67 (s, 1H), 5.65 (s, 1H), 3.94 (s, 3H), 2.78 (s, 2H),2.06 (br, 3H), 1.91 (br, 6H), 1.75 (br, 6H), 1.29 (s, 6H).

EXAMPLE 11(157)(Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.63 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.45 (brs, 1H),8.56 (d, J=2.1 Hz, 1H), 8.24 (dd, J=8.1, 2.1 Hz, 1H), 7.37 (d, J=8.1 Hz,1H), 5.85 (s, 1H), 2.94 (s, 2H), 2.12-2.06 (m, 3H), 1.94-1.90 (m, 6H),1.78-1.74 (m, 6H), 1.31 (s, 6H).

EXAMPLE 11(158)(Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.40 (brs, 1H),7.03 (d, J=8.4 Hz, 1H), 7.03 (d, J=2.4 Hz, 1H), 6.80 (dd, J=8.4, 2.4 Hz,1H), 5.57 (s, 1H), 2.99 (s, 6H), 2.73 (s, 2H), 2.31 (m, 1H), 1.93-1.10(m, 10H), 1.28 (s, 6H).

EXAMPLE 11(159)(Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.32 (brs, 1H),7.03 (d, J=8.4 Hz, 1H), 7.02 (d, J=2.4 Hz, 1H), 6.80 (dd, J=8.4, 2.4 Hz,1H), 5.54 (s, 1H), 2.99 (s, 6H), 2.73 (s, 2H), 2.47 (m, 1H), 1.97-1.40(m, 12H), 1.28 (s, 6H).

EXAMPLE 11(160)(Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.34 (brs, 1H),6.98 (d, J=8.1 Hz, 1H), 6.91 (d, J=2.4 Hz, 1H), 6.66 (dd, J=8.1, 2.4 Hz,1H), 5.56 (s, 1H), 3.76 (brs, 1H), 2.89 (s, 3H), 2.72 (s, 2H), 2.29 (m,1H), 1.93-1.10 (m, 10H), 1.27 (s, 6H).

EXAMPLE 11(161)(Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.26 (brs, 1H),6.98 (d, J=8.4 Hz, 1H), 6.91 (d, J=2.4 Hz, 1H), 6.66 (dd, J=8.4, 2.4 Hz,1H), 5.53 (s, 1H), 3.77 (brs, 1H), 2.89 (s, 3H), 2.71 (s, 2H), 2.45 (m,1H), 1.97-1.42 (m, 12H), 1.27 (s, 6H).

EXAMPLE 11(162)(Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.97 (br, 1H),8.00 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 7.05 (d, J=8.1 Hz, 1H),6.99 (d, J=2.4 Hz, 1H), 6.73 (dd, J=8.1, 2.4 Hz, 1H), 6.19 (s, 1H), 3.90(br, 1H), 2.91 (s, 3H), 2.80 (s, 2H), 1.36 (s, 6H).

EXAMPLE 11(163)(Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.23 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.88 (br, 1H),8.03-8.00 (m, 3H), 7.75 (d, J=8.5 Hz, 2H), 6.82 (s, 1H), 6.16 (s, 1H),4.02 (s, 3H), 2.95 (s, 2H), 1.39 (s, 6H).

EXAMPLE 11(164)(Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),6.99 (d, J=8.1 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.66 (dd, J=8.1, 2.4 Hz,1H), 5.70 (s, 1H), 3.78 (br, 1H), 2.89 (s, 3H), 2.72 (s, 2H), 2.05 (s,3H), 1.91 (br, 6H), 1.74 (br, 6H), 1.27 (s, 6H).

EXAMPLE 11(165)(Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.23 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.41 (br, 1H),7.93 (s, 1H), 6.76 (s, 1H), 5.67 (s, 1H), 3.99 (s, 3H), 2.86 (s, 2H),2.07 (br, 3H), 1.90 (br, 6H), 1.75 (br, 6H), 1.30 (s, 6H).

EXAMPLE 11(166)(Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.22 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.91 (s, 1H), 6.76 (s, 1H), 5.53 (s, 1H), 3.98 (s, 3H), 2.87 (s, 2H),2.30 (m, 1H), 1.89-1.80 (m, 4H), 1.70 (m, 1H), 1.57-1.16 (m, 1H).

EXAMPLE 11(167)(Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.91 (s, 1H), 6.75 (s, 1H), 5.49 (s, 1H), 3.98 (s, 3H), 2.86 (s, 2H),2.46 (m, 1H), 1.95-1.87 (m, 2H), 1.82-1.47 (m, 10H), 1.30 (s, 6H).

EXAMPLE 11(168)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.42 (brs, 1H),7.82 (d, J=1.8 Hz, 1H), 7.50 (dd, J=7.8, 1.8 Hz, 1H), 7.06 (d, J=7.8 Hz,1H), 5.71 (s, 1H), 2.78 (s, 2H), 2.10-2.04 (m, 3H), 1.93-1.89 (m, 6H),1.78-1.73 (m, 6H), 1.31 (s, 6H).

EXAMPLE 11(169)(Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.42 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.28 (br, 1H),7.59 (s, 1H), 6.62 (s, 1H), 5.55 (s, 1H), 3.87 (s, 3H), 3.45 (s, 2H),2.80 (s, 2H), 2.46 (m, 1H), 2.29 (s, 6H), 1.95-1.87 (m, 2H), 1.82-1.47(m, 10H), 1.29 (s, 6H).

EXAMPLE 11(170)(Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.86 (s, 1H), 6.67 (s, 1H), 5.51 (s, 1H), 3.94 (s, 3H), 2.79 (s, 2H),2.29 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m, 4H), 1.71-1.20 (m, 12H).

EXAMPLE 11(171)(Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.42 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.60 (s, 1H), 6.63 (s, 1H), 5.58 (s, 1H), 3.87 (s, 3H), 3.45 (s, 2H),2.81 (s, 2H), 2.37-2.25 (m, 7H), 1.88-1.79 (m, 4H), 1.71-1.20 (m, 12H).

EXAMPLE 11(172)(Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.42 (br, 1H),8.33 (s, 1H), 7.16 (s, 1H), 5.79 (s, 1H), 2.86 (s, 2H), 2.64 (s, 3H),2.07 (br, 3H), 1.91-1.90 (br, 6H), 1.76-1.75 (br, 6H), 1.31 (s, 6H).

EXAMPLE 11(173)(Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.28 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.31 (br, 1H),7.57 (s, 1H), 6.62 (s, 1H), 5.58 (s, 1H), 3.88 (s, 3H), 3.75 (s, 2H),2.80 (s, 2H), 2.47 (s, 3H), 2.29 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m,4H), 1.71-1.20 (m, 12H).

EXAMPLE 11(174)(Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.47 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.99 (br, 1H),8.02 (d, J=8.5 Hz, 2H), 7.74-7.71 (m, 3H), 6.69 (s, 1H), 6.22 (s, 1H),3.91 (s, 3H), 3.49 (s, 2H), 2.89 (s, 2H), 2.31 (s, 6H), 1.38 (s, 6H).

EXAMPLE 11(175)(Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.89 (chloroform:methanol=50:1); NMR (CDCl₃): δ 11.88 (br, 1H),8.44 (s, 1H), 8.03 (d, J=8.7 Hz, 2H), 7.76 (d, J=8.7 Hz, 2H), 7.24 (s,1H), 6.28 (s, 1H), 2.95 (s, 2H), 2.68 (s, 3H), 1.40 (s, 6H).

EXAMPLE 11(176)(Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.25 (brs, 1H),8.34 (s, 1H), 7.16 (s, 1H), 5.65 (s, 1H), 2.87 (s, 2H), 2.65 (s, 3H),2.34 (tt, J=11.4, 3.3 Hz, 1H), 1.93-1.65 (m, 5H), 1.58-1.18 (m, 1H).

EXAMPLE 11(177)(Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.17 (brs, 1H),8.34 (s, 1H), 7.16 (s, 1H), 5.62 (s, 1H), 2.86 (s, 2H), 2.65 (s, 3H),2.51 (tt, J=9.9, 3.9 Hz, 1H), 1.97-1.44 (m, 12H), 1.30 (s, 6H).

EXAMPLE 11(178)(Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.37 (brs, 1H),6.86 (s, 1H), 6.84 (s, 1H), 5.58 (s, 1H), 3.58 (brs, 1H), 2.97 (s, 3H),2.70 (s, 2H), 2.31 (tt, J=12.0, 3.3 Hz, 1H), 2.15 (s, 3H), 1.92-1.18 (m,16H).

EXAMPLE 11(179)(Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.29 (brs, 1H),6.86 (s, 1H), 6.84 (s, 1H), 5.55 (s, 1H), 3.58 (brs, 1H), 2.97 (s, 3H),2.70 (s, 2H), 2.47 (tt, J=9.9, 3.9 Hz, 1H), 2.15 (s, 3H), 1.97-1.43 (m,12H), 1.28 (s, 6H).

EXAMPLE 11(180)(Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.55 (brs, 1H),6.88 (s, 1H), 6.84 (s, 1H), 5.74 (s, 1H), 3.58 (brs, 1H), 2.97 (s, 3H),2.70 (s, 2H), 2.16 (s, 3H), 2.08-2.02 (m, 3H), 1.94-1.90 (m, 6H),1.76-1.72 (m, 6H), 1.28 (s, 6H).

EXAMPLE 11(181)(Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.86 (s, 1H), 6.67 (s, 1H), 5.48 (s, 1H), 3.94 (s, 3H), 2.78 (s, 2H),2.46 (m, 1H), 1.94-1.50 (m, 12H), 1.29 (s, 6H).

EXAMPLE 11(182)(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.07 (brs, 1H),8.09 (s, 1H), 7.63 (s, 1H), 5.64 (s, 1H), 2.94 (s, 2H), 2.35 (m, 1H),1.93-1.75 (m, 5H), 1.56-1.20 (m, 1H).

EXAMPLE 11(183)(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.37 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.22 (brs, 1H),8.10 (s, 1H), 7.63 (s, 1H), 5.78 (s, 1H), 2.94 (s, 2H), 2.12-2.05 (m,3H), 1.91-1.87 (m, 6H), 1.83-1.69 (m, 6H), 1.31 (s, 6H).

EXAMPLE 11(184)(Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=9:1); NMR (CDCl₃): δ 11.40 (br, 1H),7.83 (s, 1H), 7.04 (s, 1H), 5.69 (s, 1H), 2.74 (s, 2H), 2.42 (s, 3H),2.06 (br, 3H), 1.91-1.90 (br, 6H), 1.76-1.75 (br, 6H), 1.28 (s, 6H).

EXAMPLE 11(185)(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-cycloheptylethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.98 (brs, 1H),8.09 (s, 1H), 7.63 (s, 1H), 5.60 (s, 1H), 2.94 (s, 2H), 2.52 (m, 1H),1.96-1.44 (m, 12H), 1.31 (s, 6H).

EXAMPLE 11(186)(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.68 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 11.77 (brs, 1H),9.01 (s, 1H), 8.25 (d, J=8.4 Hz, 2H), 8.17 (s, 1H), 7.97 (d, J=8.4 Hz,2H), 6.75 (s, 1H), 3.09 (s, 2H), 1.30 (s, 6H).

EXAMPLE 11(187)(Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.98 (brs, 1H),8.01 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 6.92 (s, 1H), 6.91 (s,1H), 6.22 (s, 1H), 3.66 (brs, 1H), 2.99 (s, 3H), 2.78 (s, 2H), 2.19 (s,3H), 1.36 (s, 6H).

EXAMPLE 11(188)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.23 (brs, 1H),7.81 (d, J=2.1 Hz, 1H), 7.50 (dd, J=8.1, 2.1 Hz, 1H), 7.05 (d, J=8.1 Hz,1H), 5.57 (s, 1H), 2.78 (s, 2H), 2.31 (tt, J=11.4, 3.3 Hz, 1H),1.92-1.65 (m, 5H), 1.58-1.18 (m, 1H).

EXAMPLE 11(189)(Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.22 (br, 1H),7.83 (s, 1H), 7.04 (s, 1H), 5.55 (s, 1H), 2.74 (s, 2H), 2.41 (s, 3H),2.30 (m, 1H), 1.92-1.20 (m, 16H).

EXAMPLE 11(190)(Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.34 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.34 (br, 1H),7.07 (s, 1H), 6.90 (s, 1H), 5.55 (s, 1H), 4.33 (br, 1H), 2.98 (d, J=4.5Hz, 3H), 2.69 (s, 2H), 2.31 (m, 1H), 1.90-1.20 (m, 10H), 1.27 (s, 6H).

EXAMPLE 11(191)(Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.27 (br, 1H),7.07 (s, 1H), 6.90 (s, 1H), 5.52 (s, 1H), 4.33 (br, 1H), 2.98 (d, J=3.5Hz, 3H), 2.70 (s, 2H), 2.48 (m, 1H), 1.95-1.40 (m, 12H), 1.27 (s, 6H).

EXAMPLE 11(192)(Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.41 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.53 (br, 1H),7.07 (s, 1H), 6.92 (s, 1H), 5.71 (s, 1H), 4.33 (br, 1H), 2.99 (s, 3H),2.70 (s, 2H), 2.06 (m, 3H), 1.92 (m, 6H), 1.75 (m, 6H), 1.28 (s, 6H).

EXAMPLE 11(193)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.14 (brs, 1H),7.81 (d, J=1.8 Hz, 1H), 7.50 (dd, J=7.8, 1.8 Hz, 1H), 7.05 (d, J=7.8 Hz,1H), 5.54 (s, 1H), 2.78 (s, 2H), 2.48 (tt, J=9.9, 3.9 Hz, 1H), 1.97-1.43(m, 12H), 1.28 (s, 6H).

EXAMPLE 11(194)(Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.15 (br, 1H),7.83 (s, 1H), 7.04 (s, 1H), 5.52 (s, 1H), 2.74 (s, 2H), 2.41 (s, 3H),2.46 (m, 1H), 1.96-1.46 (m, 12H), 1.28 (s, 6H).

EXAMPLE 11(195)(Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.15 (brs, 1H),8.56 (d, J=2.1 Hz, 1H), 8.24 (dd, J=8.7, 2.1 Hz, 1H), 7.37 (d, J=8.7 Hz,1H), 5.68 (s, 1H), 2.94 (s, 2H), 2.53 (tt, J=9.9, 3.9 Hz, 1H), 1.98-1.46(m, 12H), 1.31 (s, 6H).

EXAMPLE 11(196)(Z)-2-(7-dimethylsulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.51 (brs, 1H),8.08 (d, J=1.8 Hz, 1H), 7.77 (dd, J=7.8, 1.8 Hz, 1H), 7.36 (d, J=1.8 Hz,1H), 5.79 (s, 1H), 2.92 (s, 2H), 2.77 (s, 6H), 2.10-2.03 (m, 3H),1.92-1.88 (m, 6H), 1.77-1.72 (m, 6H), 1.31 (s, 6H).

EXAMPLE 11(197)(Z)-2-(7-butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.38 (brs, 1H),8.18 (s, 1H), 7.28 (s, 1H), 5.78 (s, 1H), 4.39 (t, J=6.6 Hz, 2H), 2.83(s, 2H), 2.10-2.02 (m, 3H), 1.93-1.88 (m, 6H), 1.84-1.72 (m, 8H),1.61-1.48 (m, 8H), 1.01 (t, J=7.2 Hz, 3H).

EXAMPLE 11(198)(Z)-2-(7-butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.12 (brs, 1H),8.15 (s, 1H), 7.28 (s, 1H), 5.59 (s, 1H), 4.39 (t, J=6.6 Hz, 2H), 2.83(s, 2H), 2.48 (tt, J=9.9, 3.9 Hz, 1H), 1.96-1.43 (m, 16H), 1.29 (s, 6H),1.01 (t, J=7.2 Hz, 3H).

EXAMPLE 11(199)(Z)-2-(7-methylsulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.50 (brs, 1H),8.17 (d, J=1.8 Hz, 1H), 7.86 (dd, J=7.8, 1.8 Hz, 1H), 7.35 (d, J=7.8 Hz,1H), 5.81 (s, 1H), 4.41 (q, J=5.4 Hz, 1H), 2.91 (s, 2H), 2.72 (d, J=5.4Hz, 3H), 2.10-2.03 (m, 3H), 1.92-1.87 (m, 6H), 1.77-1.73 (m, 6H), 1.31(s, 6H).

EXAMPLE 11(200)(Z)-2-(6-chloro-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.33 (ethyl acetate:hexane=5:1); NMR (CDCl₃): δ 11.53 (br, 1H),7.21 (s, 1H), 7.19 (s, 1H), 5.68 (s, 1H), 3.99 (s, 3H), 2.74 (s, 2H),2.06 (m, 3H), 1.91 (m, 6H), 1.75 (m, 6H), 1.28 (s, 6H).

EXAMPLE 11(201)(Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=6:1); NMR (CDCl₃): δ 11.54 (br, 1H),7.10 (s, 1H), 6.93 (s, 1H), 5.69 (s, 1H), 3.91 (s, 3H), 2.73 (s, 2H),2.24 (s, 3H), 2.06 (br, 3H), 1.92-1.91 (br, 6H), 1.75 (br, 6H), 1.28 (s,6H).

EXAMPLE 11(202)(Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=6:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.09 (s, 1H), 6.92 (s, 1H), 5.54 (s, 1H), 3.90 (s, 3H), 2.73 (s, 2H),2.31 (m, 1H), 2.24 (s, 3H), 1.92-1.18 (m, 16H).

EXAMPLE 11(203)(Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=6:1); NMR (CDCl₃): δ 11.27 (br, 1H),7.08 (s, 1H), 6.92 (s, 1H), 5.51 (s, 1H), 3.90 (s, 3H), 2.73 (s, 2H),2.46 (m, 1H), 2.24 (s, 3H), 1.96-1.42 (m, 12H), 1.27 (s, 6H).

EXAMPLE 12-EXAMPLE 12(31)

By the same procedure as described in example 1 using the compoundprepared in reference example 1 or a corresponding nitrile derivative,and 2-methyl-1-phenylpropan-2-ol or a corresponding alcohol derivative,the compound of the present invention were given. In example 12(20) andexample 12(24), an operation converting to hydrochloride followed it.

EXAMPLE 12(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.78 (br, 1H),7.95-7.92 (m, 2H), 7.69 (d, J=8.5 Hz, 1H), 7.49-7.38 (m, 5H), 6.28 (br,1H), 2.87 (s, 2H), 1.37 (s, 6H).

EXAMPLE 12(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.54 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.70 (m, 1H), 7.41 (m, 1H), 7.30 (m, 1H), 7.19 (m, 1H), 5.63 (br, 1H),4.05 (m, 2H), 3.46 (dt, J=11.5, 3.5 Hz, 2H), 2.86 (s, 2H), 2.54 (m, 1H),1.90-1.70 (m, 4H), 1.31 (s, 6H).

EXAMPLE 12(2)(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.35 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.31 (br, 1H),7.70 (dd, J=9.0, 5.5 Hz, 1H), 6.98 (ddd, J=9.0, 9.0, 2.5 Hz, 1H), 6.88(dd, J=9.0, 2.5 Hz, 1H), 5.57 (s, 1H), 2.82 (s, 2H), 2.28 (m, 1H),1.95-1.20 (m, 10H), 1.29 (s, 6H).

EXAMPLE 12(3)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.40 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.26 (br, 1H),7.63 (d, J=9.0 Hz, 1H), 7.26 (dd, J=9.0, 2.5 Hz, 1H), 7.17 (d, J=2.5 Hz,1H), 5.58 (s, 1H), 2.81 (s, 2H), 2.29 (m, 1H), 1.95-1.20 (m, 10H), 1.29(s, 6H).

EXAMPLE 12(4)(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.22 (br, 1H),7.70 (dd, J=9.0, 5.5 Hz, 1H), 6.97 (ddd, J=9.0, 9.0, 2.5 Hz, 1H), 6.87(dd, J=9.0, 2.5 Hz, 1H), 5.53 (s, 1H), 2.82 (s, 2H), 2.45 (m, 1H),2.00-1.40 (m, 12H), 1.29 (s, 6H).

EXAMPLE 12(5)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.42 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.17 (br, 1H),7.63 (d, J=8.5 Hz, 1H), 7.25 (dd, J=8.5, 2.0 Hz, 1H), 7.17 (d, J=2.0 Hz,1H), 5.55 (s, 1H), 2.80 (s, 2H), 2.45 (m, 1H), 2.00-1.40 (m, 12H), 1.29(s, 6H).

EXAMPLE 12(6)(Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.42 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.77 (br, 1H),7.30 (dd, J=7.5, 7.5 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H), 6.77 (d, J=7.5 Hz,1H), 6.20 (s, 1H), 3.92 (s, 3H), 2.79 (s, 2H), 2.26 (m, 1H), 1.95-1.10(m, 10H), 1.26 (s, 6H).

EXAMPLE 12(7)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.32 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.33 (br, 1H),7.65 (d, J=8.5 Hz, 1H), 6.80 (dd, J=8.5, 2.5 Hz, 1H), 6.67 (d, J=2.5 Hz,1H), 5.55 (s, 1H), 3.85 (s, 3H), 2.80 (s, 2H), 2.27 (m, 1H), 1.95-1.10(m, 10H), 1.29 (s, 6H).

EXAMPLE 12(8)(Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.46 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.67 (br, 1H),7.29 (dd, J=7.5, 7.5 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H), 6.76 (d, J=7.5 Hz,1H), 6.17 (s, 1H), 3.91 (s, 3H), 2.78 (s, 2H), 2.42 (m, 1H), 2.00-1.40(m, 12H), 1.26 (s, 6H).

EXAMPLE 12(9)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.25 (br, 1H),7.65 (d, J=8.5 Hz, 1H), 6.80 (dd, J=8.5, 3.0 Hz, 1H), 6.67 (d, J=3.0 Hz,1H), 5.52 (s, 1H), 3.85 (s, 3H), 2.80 (s, 2H), 2.43 (m, 1H), 2.00-1.40(m, 12H), 1.29 (s, 6H).

EXAMPLE 12(10)(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.63 (br, 1H),7.74-7.68 (m, 2H), 7.49-7.25 (m, 4H), 7.03-6.95 (m, 2H), 6.26 (s, 1H),3.92 (s, 3H), 1.31 (br, 12H).

EXAMPLE 12(11)(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.69 (dd, J=7.5, 1.0 Hz, 1H), 7.47-7.37 (m, 2H), 7.29-7.24 (m, 1H), 5.59(s, 1H), 2.35-2.24 (m, 1H), 1.91-1.79 (m, 4H), 1.69-1.64 (m, 1H),1.55-1.19 (m, 17H).

EXAMPLE 12(12)(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.68 (dd, J=8.0, 1.0 Hz, 1H), 7.47-7.37 (m, 2H), 7.29-7.24 (m, 1H), 5.56(s, 1H), 2.50-2.41 (m, 1H), 1.96-1.90 (m, 2H), 1.83-1.43 (m, 10H), 1.26(br, 12H).

EXAMPLE 12(13)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(isoquinolin-1-yl)ethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.79 (br, 1H),8.86 (d, J=8.0 Hz, 1H), 8.55 (d, J=5.5 Hz, 1H), 7.88-7.84 (m, 2H),7.72-7.59 (m, 3H), 7.42 (dt, J=1.0, 7.0 Hz, 1H), 7.33-7.27 (m, 1H), 7.21(d, J=7.5 Hz, 1H), 6.54 (s, 1H), 2.94 (s, 2H), 1.42 (s, 6H).

EXAMPLE 12(14)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(quinolin-4-yl)ethan-1-one

TLC: Rf0.11 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.84 (br, 1H),8.96 (d, J=4.5 Hz, 1H), 8.42 (d, J=7.5 Hz, 1H), 8.14 (d, J=8.0 Hz, 1H),7.75-7.69 (m, 2H), 7.57 (t, J=8.0 Hz, 1H), 7.51 (d, J=4.5 Hz, 1H), 7.45(t, J=7.5 Hz, 1H), 7.33-7.23 (m, 2H), 6.02 (s, 1H), 2.97 (s, 2H), 1.43(s, 6H).

EXAMPLE 12(15)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.63 (br, 1H),7.68-7.65 (m, 2H), 7.37 (ddd, J=8.0, 7.5, 2.0 Hz, 1H), 7.29-7.26 (m,1H), 7.20 (d, J=2.0 Hz, 1H), 7.03-6.95 (m, 2H), 6.23 (s, 1H), 3.91 (s,3H), 2.86 (s, 2H), 1.36 (s, 6H).

EXAMPLE 12(16)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-chlorophenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.49 (br, 10H),7.65 (d, J=8.5 Hz, 1H), 7.54-7.51 (m, 1H), 7.42-7.39 (m, 1H), 7.32-7.27(m, 3H), 7.21 (d, J=2.0 Hz, 1H), 5.93 (s, 10H), 2.89 (s, 2H), 1.38 (s,6H).

EXAMPLE 12(17)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(quinolin-8-yl)ethan-1-one

TLC: Rf0.17 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.80 (br, 1H),9.05 (dd, J=4.0, 2.0 Hz, 1H), 8.19 (dd, J=8.0, 2.0 Hz, 1H), 7.98 (dd,J=7.5, 1.5 Hz, 1H), 7.85 (dd, J=8.0, 1.5 Hz, 1H), 7.74 (d, J=7.5 Hz,1H), 7.58 (dd, J=8.0, 7.5 Hz, 1H), 7.44-7.37 (m, 2H), 7.29-7.24 (m, 1H),7.20 (d, J=7.5 Hz, 1H), 6.35 (s, 1H), 2.92 (s, 2H), 1.40 (s, 6H).

EXAMPLE 12(18)(Z)-2-(6,8-dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.98 (brs, 1H),7.93-7.89 (m, 2H), 7.47-7.41 (m, 4H), 7.14 (m, 1H), 6.79 (s, 1H), 2.83(s, 2H), 1.33 (s, 6H).

EXAMPLE 12(19)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-ethoxyphenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.70 (br, 1H),7.81 (dd, J=7.5, 2.0 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.43-7.27 (m, 3H),7.20 (d, J=7.5 Hz, 1H), 7.01 (dt, J=1.0, 7.5 Hz, 1H), 6.95 (dd, J=7.5,1.0 Hz, 1H), 6.55 (s, 1H), 4.15 (q, J=7.0 Hz, 2H), 2.90 (s, 2H), 1.49(t, J=7.0 Hz, 3H), 1.36 (s, 6H).

EXAMPLE 12(20)2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)propan-1-one,hydrochloride

TLC: Rf0.40 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 7.92 (d, J=7.5Hz, 1H), 7.67 (dd, J=7.5, 7.5 Hz, 1H), 7.42 (dd, J=7.5, 7.5 Hz, 1H),7.34 (d, J=7.5 Hz, 1H), 5.80 (q, J=7.0 Hz, 1H), 3.03 (s, 2H), 2.02 (m,3H), 1.87 (m, 6H), 1.80-1.55 (m, 15H).

EXAMPLE 12(21)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-chloro-2-methoxyphenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.70 (br, 1H),7.73 (d, J=7.5 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H),7.31 (t, J=7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 6.99 (dd, J=8.0, 2.0 Hz,1H), 6.94 (d, J=2.0 Hz, 1H), 6.25 (s, 1H), 3.91 (s, 3H), 2.89 (s, 2H),1.35 (s, 6H).

EXAMPLE 12(22)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxy-4-methylthiophenyl)ethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.70 (br, 1H),7.74 (d, J=7.5 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.40 (t, J=7.5 Hz, 1H),7.30 (t, J=7.5 Hz, 1H), 7.19 (d, J=7.5 Hz, 1H), 6.87 (dd, J=8.0, 2.0 Hz,1H), 6.83 (d, J=2.0 Hz, 1H), 6.34 (s, 1H), 3.92 (s, 3H), 2.89 (s, 2H),2.52 (s, 3H), 1.35 (s, 6H).

EXAMPLE 12(23)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxy-4-mesylphenyl)ethan-1-one

TLC: Rf0.15 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.73 (br, 1H),7.79 (d, J=8.0 Hz, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.57 (dd, J=8.0, 1.5 Hz,1H), 7.50 (d, J=1.5 Hz, 1H), 7.44 (t, J=7.5 Hz, 1H), 7.32 (t, J=7.5 Hz,1H), 7.22 (d, J=7.5 Hz, 1H), 6.14 (s, 1H), 3.98 (s, 3H), 3.08 (s, 3H),2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 12(24)2-(6-fluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-phenylpropan-1-one,hydrochloride

TLC: Rf0.35 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 8.14 (d, J=8.0Hz, 2H), 7.86 (dd, J=8.5, 5.0 Hz, 1H), 7.54 (m, 1H), 7.46 (m, 2H), 7.05(ddd, J=8.5, 8.5, 2.5 Hz, 1H), 6.96 (dd, J=8.5, 2.5 Hz, 1H), 6.34 (q,J=6.5 Hz, 1H), 3.04 (d, J=17.0 Hz, 1H), 2.85 (d, J=17.0 Hz, 1H), 1.79(d, J=6.5 Hz, 3H), 1.71 (s, 3H), 1.46 (s, 3H).

EXAMPLE 12(25)(Z)-2-(6,7-dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-phenylethan-1-one

TLC: Rf0.23 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.72 (br, 1H),7.96-7.93 (m, 2H), 7.88 (s, 1H), 7.48-7.43 (m, 3H), 7.33 (s, 1H), 6.24(s, 1H), 2.85 (s, 2H), 1.36 (s, 6H).

EXAMPLE 12(26)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-bromo-2-methoxyphenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.70 (br, 1H),7.72 (d, J=7.5 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H),7.31 (t, J=7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.15 (dd, J=8.0, 2.0 Hz,1H), 7.10 (d, J=2.0 Hz, 1H), 6.24 (s, 1H), 3.91 (s, 3H), 2.89 (s, 2H),1.35 (s, 6H).

EXAMPLE 12(27)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-bromo-2-chlorophenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.56 (br, 1H),7.71 (d, J=7.5 Hz, 1H), 7.58 (m, 1H), 7.46-7.41 (m, 3H), 7.31 (t, J=7.5Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 5.93 (s, 1H), 2.91 (s, 2H), 1.37 (s,6H).

EXAMPLE 12(28)(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-cyclohexylethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.56 (d, J=8.5 Hz, 1H), 7.42 (dd, J=8.5, 2.0 Hz, 1H), 7.33 (d, J=2.0 Hz,1H), 5.59 (s, 1H), 2.81 (s, 2H), 2.29 (m, 1H), 1.89-1.79 (m, 4H), 1.69(m, 1H), 1.55-1.24 (m, 1H).

EXAMPLE 12(29)(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.56 (d, J=8.5 Hz, 1H), 7.42 (dd, J=8.5, 2.0 Hz, 1H), 7.33 (d, J=2.0 Hz,1H), 5.55 (s, 1H), 2.81 (s, 2H), 2.45 (m, 1H), 1.95-1.85 (m, 2H),1.82-1.45 (m, 10H), 1.29 (s, 6H).

EXAMPLE 12(30)(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.42 (br, 1H),7.58 (d, J=8.5 Hz, 1H), 7.42 (dd, J=8.5, 2.0 Hz, 1H), 7.33 (d, J=2.0 Hz,1H), 5.74 (s, 1H), 2.81 (s, 2H), 2.05 (br, 3H), 1.90 (br, 6H), 1.74 (br,6H), 1.29 (s, 6H).

EXAMPLE 12(31)(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.82 (br, 1H),9.13 (dd, J=2.0, 1.0 Hz, 1H), 8.67 (dd, J=5.0, 2.0 Hz, 1H), 8.20 (ddd,J=8.0, 2.0, 2.0 Hz, 1H), 7.69 (d, J=8.5 Hz, 1H), 7.50 (dd, J=8.5, 2.0Hz, 1H), 7.40-7.35 (m, 2H), 6.24 (s, 1H), 2.89 (s, 2H), 1.38 (s, 6H).

EXAMPLE 13(Z)-2-(6-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 12 (356 mg) in ether(10 ml) was added n-butyl lithium (1.4 ml, 1.6M in hexane) dropwise andten minutes later it was warmed to 0° C. and the mixture was stirred for30 minutes. To the reaction mixture was added dimethylformamide (0.20ml) at −78° C. and was stirred for 30 minutes at 0° C. To the reactionmixture was added a saturated aqueous solution of ammonium chloride andwas extracted with ethyl acetate. The extract was washed with water andbrine, dried over anhydrous magnesium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=20:1→5:1) to give the compound of the presentinvention (165 mg) having the following physical data.

TLC: Rf0.34 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.75 (br, 1H),10.07 (s, 1H), 8.01-7.94 (m, 3H), 7.85 (d, J=8.0 Hz, 1H), 7.74 (s, 1H),7.48-7.42 (m, 3H), 6.38 (s, 1H), 2.99 (s, 2H), 1.38 (s, 6H).

EXAMPLE 13-EXAMPLE 13(16)

By the same procedure as described in example 13, using the compoundprepared in example 11(7), example 11(70), example 11(81), example12(26), example 11(119), example 11(153), example 11(154), example11(156), example 11(168), example 11(170), example 11(181), example11(184), example 11(188), example 11(189), example 11(193) or example11(194) in place of the compound prepared in example 12, the followingcompounds of the present invention were given.

EXAMPLE 13(1)(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.82 (br, 1H),10.08 (s, 1H), 8.34 (d, J=1.5 Hz, 1H), 7.99-7.93 (m, 3H), 7.49-7.40 (m,4H), 6.42 (s, 1H), 2.99 (s, 2H), 1.38 (s, 6H).

EXAMPLE 13(2)(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.76 (br, 1H),10.00 (s, 1H), 8.48 (m, 1H), 8.22 (d, J=1.5 Hz, 1H), 7.95-7.85 (m, 3H),7.72 (dd, J=7.0, 1.5 Hz, 1H), 7.55-7.45 (m, 3H), 7.42 (d, J=8.0 Hz, 1H),6.19 (s, 1H), 3.04 (s, 2H), 1.44 (s, 6H).

EXAMPLE 13(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-formylphenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=3:1), NMR (CDCl₃): δ 11.99 (br, 1H),10.08 (s, 1H), 8.08 (d, J=8.5 Hz, 2H), 7.95 (d, J=8.5 Hz, 2H), 7.84 (d,J=7.5 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.24 (d,J=7.5 Hz, 1H), 6.34 (s, 1H), 2.93 (s, 2H), 1.39 (s, 6H).

EXAMPLE 13(4)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-formyl-2-methoxyphenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.76 (br, 1H),10.02 (s, 1H), 7.79 (d, J=7.5 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.51 (dd,J=7.5, 1.0 Hz, 1H), 7.48 (d, J=1.0 Hz, 1H), 7.43 (t, J=7.5 Hz, 1H), 7.31(t, J=7.5 Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 6.20 (s, 1H), 3.89 (s, 3H),2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 13(5)(Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.43 (br, 1H),10.47 (s, 1H), 8.25 (s, 1H), 7.30 (s, 1H), 5.83 (s, 1H), 2.87 (s, 2H),2.06 (m, 3H), 1.90 (m, 6H), 1.76 (m, 6H), 1.30 (s, 6H).

EXAMPLE 13(6)(Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.36 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.19 (br, 1H),10.46 (s, 1H), 8.25 (s, 1H), 7.29 (s, 1H), 5.70 (s, 1H), 2.87 (s, 2H),2.35 (m, 1H), 1.90-1.20 (m, 10H), 1.30 (s, 6H).

EXAMPLE 13(7)(Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.11 (br, 1H),10.45 (s, 1H), 8.24 (s, 1H), 7.29 (s, 1H), 5.66 (s, 1H), 2.86 (s, 2H),2.48 (m, 1H), 1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 13(8)(Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.22 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.52 (br, 1H),10.45 (s, 1H), 8.20 (s, 1H), 6.78 (s, 1H), 5.80 (s, 1H), 3.99 (s, 3H),2.87 (s, 2H), 2.05 (br, 3H), 1.91 (br, 6H), 1.75 (br, 6H), 1.30 (s, 6H).

EXAMPLE 13(9)(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.64 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.49 (brs, 1H),10.06 (s, 1H), 8.22 (d, J=1.5 Hz, 1H), 7.90 (dd, J=7.8, 1.5 Hz, 1H),7.36 (d, J=7.8 Hz, 1H), 5.87 (s, 1H), 2.93 (s, 2H), 2.11-2.04 (m, 3H),1.94-1.90 (m, 6H), 1.78-1.73 (m, 6H), 1.31 (s, 6H).

EXAMPLE 13(10)(Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-13,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.10 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.27 (br, 1H),10.44 (s, 1H), 8.19 (s, 1H), 6.77 (s, 1H), 5.67 (s, 1H), 3.99 (s, 3H),2.87 (s, 2H), 2.31 (m, 1H), 1.90-1.79 (m, 4H), 1.70 (m, 1H), 1.56-1.20(m, 1H).

EXAMPLE 13(11)(Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-cycloheptylethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.20 (br, 1H),10.44 (s, 1H), 8.19 (s, 1H), 6.77 (s, 1H), 5.64 (s, 1H), 3.99 (s, 3H),2.87 (s, 2H), 2.47 (m, 1H), 1.94-1.45 (m, 12H), 1.30 (s, 6H).

EXAMPLE 13(12)(Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=6:1); NMR (CDCl₃): δ 11.48 (br, 1H),10.31 (s, 1H), 8.13 (s, 1H), 7.09 (s, 1H), 5.84 (s, 1H), 2.86 (s, 2H),2.70 (s, 3H), 2.07-2.06 (br, 3H), 1.93-1.92 (br, 6H), 1.75 (br, 6H),1.30 (s, 6H).

EXAMPLE 13(13)(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.27 (brs, 1H),10.04 (s, 1H), 8.22 (d, J=1.5 Hz, 1H), 7.90 (dd, J=7.5, 1.5 Hz, 1H),7.36 (d, J=7.5 Hz, 1H), 5.73 (s, 1H), 2.93 (s, 2H), 2.34 (tt, J=11.7,3.3 Hz, 1H), 1.94-1.66 (m, 5H), 1.58-1.24 (m, 1H).

EXAMPLE 13(14)(Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.26 (br, 1H),10.29 (s, 1H), 8.13 (s, 1H), 7.09 (s, 1H), 5.71 (s, 1H), 2.86 (s, 2H),2.70 (s, 3H), 2.33 (m, 1H), 1.90-1.27 (m, 16H).

EXAMPLE 13(15)(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.19 (brs, 1H),10.05 (s, 1H), 8.21 (d, J=1.5 Hz, 1H), 7.89 (dd, J=7.5, 1.5 Hz, 1H),7.36 (d, J=7.5 Hz, 1H), 5.70 (s, 1H), 2.93 (s, 2H), 2.51 (tt, J=9.9, 3.9Hz, 1H), 1.98-1.46 (m, 12H), 1.31 (s, 6H).

EXAMPLE 13(16)(Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.18 (br, 1H),10.29 (s, 1H), 8.13 (s, 1H), 7.08 (s, 1H), 5.67 (s, 1H), 2.86 (s, 2H),2.70 (s, 3H), 2.50 (m, 1H), 1.98-1.54 (m, 12H), 1.30 (s, 6H).

EXAMPLE 14(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-aminophenyl)ethan-1-one

To a suspension of the compound prepared in example 11(54) (312 mg) inacetic acid (10 ml) was added steel powder (1.35 g) and the mixture wasstirred for 40 minutes at 70° C. The reaction mixture was allowed tocool and thereto were added ice and 1N hydrochloric acid and filteredover celite. The filtrate was extracted. The organic layer was extractedwith 2N hydrochloric acid. The combined aqueous layer was alkalifiedwith a 5N aqueous solution of sodium hydroxide and extracted witht-butyl methyl ether. The extract was washed with water and brine, driedover anhydrous magnesium sulfate and concentrated to give the compoundof the present invention (229 mg) having the following physical data.

TLC: Rf0.15 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.67 (br, 1H),7.86-7.81 (m, 3H), 7.41 (t, J=7.5 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 7.20(d, J=7.5 Hz, 1H), 6.71-6.67 (m, 2H), 6.29 (s, 1H), 4.02-3.84 (br, 2H),2.88 (s, 2H), 1.34 (s, 6H).

EXAMPLE 14(1)-EXAMPLE 14(15)

By the same procedure as described in example 14 using the compoundprepared in example 11(52), example 11(53), example 11(100), example11(126) to 11(130), example 11(150), example 11(157), example 11(195),example 11(172) or example 11(175) to 11(177) in place of the compoundprepared in example 11(54), the following compounds of the presentinvention were given.

EXAMPLE 14(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-aminophenyl)ethan-1-one

TLC: Rf0.14 (chloroform:methanol=10:1); NMR (CDCl₃): δ 8.43 (dd, J=8.0,1.5 Hz, 1H), 7.62-7.56 (m, 2H), 7.48-7.32 (m, 5H), 6.35 (s, 1H), 2.82(br, 2H), 1.43 (s, 6H).

EXAMPLE 14(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-aminophenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.80 (br, 1H),7.82 (d, J=7.5 Hz, 1H), 7.43 (t, J=7.5 Hz, 1H), 7.36-7.27 (m, 3H),7.24-7.19 (m, 2H), 6.78 (ddd, J=8.0, 2.5, 1.0 Hz, 1H), 6.29 (s, 1H),3.79 (br, 2H), 2.90 (s, 2H), 1.36 (s, 6H).

EXAMPLE 14(3)(Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (brs, 1H),7.97-7.92 (m, 2H), 7.46-7.41 (m, 3H), 7.14 (d, J=2.7 Hz, 1H), 7.00 (d,J=7.8 Hz, 1H), 6.77 (dd, J=7.8, 2.7 Hz, 1H), 6.24 (s, 1H), 3.74 (brs,2H), 2.78 (s, 2H), 1.35 (s, 6H).

EXAMPLE 14(4)(Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.44 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.93 (br, 1H),8.01 (d, J=8.5 Hz, 2H), 7.71 (d, J=8.5 Hz, 2H), 7.11 (d, J=2.5 Hz, 1H),7.02 (d, J=8.0 Hz, 1H), 6.80 (dd, J=8.0, 2.5 Hz, 1H), 6.18 (s, 1H), 3.77(br, 2H), 2.79 (s, 2H), 1.36 (s, 6H).

EXAMPLE 14(5)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.58 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.26 (br, 1H),7.11 (s, 1H), 7.06 (s, 1H), 5.51 (s, 1H), 4.06 (br, 2H), 2.69 (s, 2H),2.27 (m, 1H), 1.95-1.20 (m, 10H), 1.27 (s, 6H).

EXAMPLE 14(6)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.63 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.17 (br, 1H),7.10 (s, 1H), 7.06 (s, 1H), 5.47 (s, 1H), 4.06 (br, 2H), 2.69 (s, 2H),2.44 (m, 1H), 2.00-1.40 (m, 12H), 1.27 (s, 6H).

EXAMPLE 14(7)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.40 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.90 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 7.19 (s, 1H), 7.13 (s,1H), 6.14 (s, 1H), 4.14 (br, 2H), 2.78 (s, 2H), 1.36 (s, 6H).

EXAMPLE 14(8)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.68 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.43 (br, 1H),7.12 (s, 1H), 7.07 (s, 1H), 5.65 (s, 1H), 4.08 (br, 2H), 2.69 (s, 2H),2.05 (m, 3H), 1.90 (m, 6H), 1.74 (m, 6H), 1.27 (s, 6H).

EXAMPLE 14(9)(Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-cyclohexylethan-1-one

TLC: Rf0.15 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.29 (br, 1H),7.02 (d, J=2.5 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.73 (dd, J=8.0, 2.5 Hz,1H), 5.54 (s, 1H), 3.69 (br, 2H), 2.71 (s, 2H), 2.28 (m, 1H), 1.95-1.20(m, 10H), 1.27 (s, 6H).

EXAMPLE 14(10)(Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan1-yl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.46 (brs, 1H),7.04 (d, J=2.4 Hz, 1H), 6.95 (d, J=8.4 Hz, 1H), 6.73 (dd, J=8.4, 2.4 Hz,1H), 5.69 (s, 1H), 3.72 (brs, 2H), 2.71 (s, 2H), 2.05 (brs, 3H),1.93-1.89 (m, 6H), 1.77-1.72 (m, 6H), 1.27 (s, 6H).

EXAMPLE 14(11)(Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.20 (brs, 1H),7.02 (d, J=2.4 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.73 (dd, J=7.8, 2.4 Hz,1H), 5.51 (s, 1H), 3.69 (brs, 2H), 2.71 (s, 2H), 2.44 (m, 1H), 1.97-1.42(m, 12H), 1.27 (s, 6H).

EXAMPLE 14(12)(Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.21 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.45 (br, 1H),7.02 (s, 1H), 6.84 (s, 1H), 5.67 (s, 1H), 3.66 (br, 2H), 2.69 (s, 2H),2.19 (s, 3H), 2.05 (br, 3H), 1.92-1.91 (br, 6H), 1.75-1.74 (br, 6H),1.27 (s, 6H).

EXAMPLE 14(13)(Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 11.91 (br, 1H),8.01 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 7.09 (s, 1H), 6.91 (s,1H), 6.17 (s, 1H), 3.71 (br, 2H), 2.78 (s, 2H), 2.22 (s, 3H), 1.36 (s,6H).

EXAMPLE 14(14)(Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.37 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.28 (brs, 1H),7.01 (s, 1H), 6.84 (s, 1H), 5.53 (s, 1H), 3.62 (brs, 2H), 2.69 (s, 2H),2.27 (tt, J=12.0, 3.3 Hz, 1H), 2.19 (s, 3H), 1.92-1.18 (m, 16H).

EXAMPLE 14(15)(Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.19 (brs, 1H),7.00 (s, 1H), 6.84 (s, 1H), 5.49 (s, 1H), 3.62 (brs, 2H), 2.69 (s, 2H),2.43 (tt, J=9.9, 3.6 Hz, 1H), 2.19 (s, 3H), 1.96-1.42 (m, 12H), 1.27 (s,6H).

EXAMPLE 15(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 12 (356 mg) in ether(10 ml) was added t-butyl lithium (2.2 ml, 1.5M in pentane) dropwise andfive minutes later carbon dioxide gas was bubbled to it. The reactionmixture was allowed to warm to room temperature and thereto were addedwater and ethyl acetate and extracted. The organic layer was extractedwith water. The combined aqueous layer was azeotroped. To the givensolid was added ethanol and filtered and the filtrate was concentrated.The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=1:1) to give the compound of the present invention(19 mg) having the following physical data.

TLC: Rf0.25 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.76 (br, 1H),8.06 (dd, J=8.0, 1.5 Hz, 1H), 7.97-7.92 (m, 4H), 7.49-7.42 (m, 3H), 6.38(s, 1H), 2.98 (s, 2H), 1.39 (s, 6H).

EXAMPLE 15(1)-EXAMPLE 15(14)

By the same procedure as described in example 15 using the compound ofexample 11(7), example 11(168), example 12(28), example 12(29), example11(188), example 11(193), example 11(181), example 11(156), example11(189), example 11(170), example 11(184), example 111(194), example12(30) or example 12(31) in place of the compound prepared in example12, the compounds of the present invention were given.

EXAMPLE 15(1)(Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.84 (br, 1H),8.57 (d, J=2.0 Hz, 1H), 8.16 (dd, J=8.0, 2.0 Hz, 1H), 8.00-7.96 (m, 2H),7.48-7.44 (m, 3H), 7.35 (d, J=8.0 Hz, 1H), 6.43 (s, 1H), 2.99 (s, 2H),1.39 (s, 6H).

EXAMPLE 15(2)(Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.27 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.52 (br, 1H),8.45 (d, J=1.5 Hz, 1H), 8.12 (dd, J=8.0, 1.5 Hz, 1H), 7.31 (d, J=8.0 Hz,1H), 5.87 (s, 1H), 2.92 (s, 2H), 2.08 (br, 3H), 1.93 (br, 6H), 1.77 (br,6H), 1.31 (s, 6H).

EXAMPLE 15(3)(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.36 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.25 (br, 1H),8.01 (dd, J=8.0, 1.5 Hz, 1H), 7.92 (d, J=1.5 Hz, 1H), 7.81 (d, J=8.0 Hz,1H), 5.69 (s, 1H), 2.91 (s, 2H), 2.33 (m, 1H), 1.91-1.80 (m, 4H), 1.72(m, 1H), 1.50-1.20 (m, 1H).

EXAMPLE 15(4)(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.39 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.16 (br, 1H),8.02 (dd, J=8.5, 1.5 Hz, 1H), 7.92 (d, J=1.5 Hz, 1H), 7.81 (d, J=8.5 Hz,1H), 5.66 (s, 1H), 2.91 (s, 2H), 2.50 (m, 1H), 1.97-1.90 (m, 2H),1.84-1.45 (m, 10H), 1.31 (s, 6H).

EXAMPLE 15(5)(Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.29 (brs, 1H),8.45 (d, J=1.8 Hz, 1H), 8.11 (dd, J=7.8, 1.8 Hz, 1H), 7.30 (d, J=7.8 Hz,1H), 5.73 (s, 1H), 2.92 (s, 2H), 2.35 (m, 1H), 1.95-1.65 (m, 5H),1.54-1.20 (m, 1H).

EXAMPLE 15(6)(Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.22 (brs, 1H),8.45 (d, J=1.8 Hz, 1H), 8.12 (dd, J=7.8, 1.8 Hz, 1H), 7.30 (d, J=7.8 Hz,1H), 5.71 (s, 1H), 2.92 (s, 2H), 2.52 (tt, J=9.9, 3.6 Hz, 1H), 1.99-1.45(m, 12H), 1.31 (s, 6H).

EXAMPLE 15(7).(Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.09 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.17 (br, 1H),10.40 (br, 1H), 8.54 (s, 1H), 6.85 (s, 1H), 5.67 (s, 1H), 4.13 (s, 3H),2.89 (s, 2H), 2.49 (tt, J=10.0, 4.0 Hz, 1H), 1.94-1.87 (m, 2H),1.83-1.48 (m, 10H), 1.30 (s, 6H).

EXAMPLE 15(8)(Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.10 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.50 (br, 1H),10.40 (br, 1H), 8.55 (s, 1H), 6.85 (s, 1H), 5.83 (s, 1H), 4.14 (s, 3H),2.89 (s, 2H), 2.06 (br, 3H), 1.91 (br, 6H), 1.75 (br, 6H), 1.31 (s, 6H).

EXAMPLE 15(9)(Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.16 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.29 (br, 1H),8.41 (s, 1H), 7.10 (s, 1H), 5.69 (s, 1H), 2.85 (s, 2H), 2.68 (s, 3H),2.34 (m, 1H), 1.91-1.20 (m, 16H).

EXAMPLE 15(10)(Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.07 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.23 (br, 1H),10.40 (br, 1H), 8.54 (s, 1H), 6.85 (s, 1H), 5.71 (s, 1H), 4.13 (s, 3H),2.89 (s, 2H), 2.32 (tt, J=11.5, 3.5 Hz, 1H), 1.89-1.79 (m, 4H), 1.70 (m,1H), 1.56-1.21 (m, 1H).

EXAMPLE 15(11)(Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.51 (br, 1H),8.41 (s, 1H), 7.10 (s, 1H), 5.83 (s, 1H), 2.85 (s, 2H), 2.69 (s, 3H),2.07-2.05 (br, 3H), 1.93-1.92 (br, 6H), 1.76-1.75 (br, 6H), 1.31 (s,6H).

EXAMPLE 15(12)(Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.22 (br, 1H),8.42 (s, 1H), 7.10 (s, 1H), 5.66 (s, 1H), 2.85 (s, 2H), 2.69 (s, 3H),2.50 (m, 1H), 1.98-1.64 (m, 12H), 1.31 (s, 6H).

EXAMPLE 15(13)(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.08 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.39 (br, 1H),7.99 (br, 1H), 7.88 (s, 1H), 7.78 (br, 1H), 5.82 (s, 1H), 2.86 (s, 2H),2.06 (br, 3H), 1.91 (br, 6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 15(14)(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.31 (methylene chloride:methanol=10:1); NMR (CDCl₃+a few dropsof CD₃OD): δ 9.17 (d, J=1.5 Hz, 1H), 8.67 (dd, J=4.5, 1.5 Hz, 1H), 8.27(ddd, J=8.5, 1.5, 1.5 Hz, 1H), 8.06 (dd, J=8.5, 2.0 Hz, 1H), 7.94-7.91(m, 2H), 7.44 (dd, J=8.5, 4.5 Hz, 1H), 6.35 (s, 1H), 2.98 (s, 2H), 1.39(s, 6H).

EXAMPLE 16-EXAMPLE 16(6)

By the same procedure as described in example 5 using the compoundprepared in example 12(10), example 11(57), example 11(2), example11(123), example 11(200), example 11(64) or example 11(32) in place ofthe compound prepared in example 1(18), the compounds of the presentinvention were given.

EXAMPLE 16(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-hydroxyphenyl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 13.65 (s, 1H),11.29 (br, 1H), 7.81 (d, J=7.5 Hz, 1H), 7.76 (dd, J=8.0, 1.5 Hz, 1H),7.54-7.49 (m, 1H), 7.44 (dd, J=8.0, 1.5 Hz, 1H), 7.38-7.30 (m, 2H), 6.94(dd, J=7.0, 1.5 Hz, 1H), 6.83 (dt, J=1.5, 7.5 Hz, 1H), 6.30 (s, 1H),1.31 (br, 12H).

EXAMPLE 16(1)(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

TLC: Rf0.44 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.70 (br, 1H),8.45 (m, 1H), 7.90-7.80 (m, 2H), 7.62 (dd, J=7.0, 1.0 Hz, 1H), 7.50-7.40(m, 2H), 7.38 (dd, J=8.0, 7.0 Hz, 1H), 7.10 (d, J=2.5 Hz, 1H), 7.00 (d,J=8.5 Hz, 1H), 6.85 (dd, J=8.5, 2.5 Hz, 1H), 6.04 (br, 1H), 5.94 (br,1H), 2.79 (s, 2H), 1.34 (s, 6H).

EXAMPLE 16(2)(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.14 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.76 (br, 1H),7.91 (m, 2H), 7.50-7.35 (m, 3H), 7.26 (d, J=2.5 Hz, 1H), 7.05 (d, J=8.5Hz, 1H), 6.93 (dd, J=8.5, 2.5 Hz, 1H), 6.24 (s, 1H), 5.95 (s, 1H), 2.78(s, 2H), 1.30 (s, 6H).

EXAMPLE 16(3)(Z)-2-(5-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 11.87 (brs,1H), 9.80 (s, 1H), 7.98-7.93 (m, 2H), 7.52 (d, J=8.4 Hz, 1H), 7.48-7.40(m, 3H), 7.18 (t, J=8.4 Hz, 1H), 7.01 (d, J=8.4 Hz, 1H), 6.39 (s, 1H),2.81 (s, 2H), 1.28 (s, 6H).

EXAMPLE 16(4)(Z)-2-(6-chloro-7-hydroxy-3,3-dimethyl-3′,4-dihydro-(2H)-isoquinolin-1-ylidene)1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (ethyl acetate:hexane=5:1); NMR (CDCl₃): δ 11.38 (br, 1H),7.39 (s, 1H), 7.14 (s, 1H), 5.70 (s, 1H), 5.60 (br, 1H), 2.73 (s, 2H),2.04 (m, 3H), 1.89 (m, 6H), 1.73 (m, 6H), 1.28 (s, 6H).

EXAMPLE 16(5)(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.18 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.42 (br, 1H),7.21 (d, J=2.4 Hz, 1H), 7.04 (d, J=8.1 Hz, 1H), 6.88 (dd, J=2.4, 8.1 Hz,1H), 5.71 (s, 1H), 5.16 (br, 1H), 2.75 (s, 2H), 2.05 (br, 3H), 1.91-1.90(br, 6H), 1.73 (br, 6H), 1.27 (s, 6H).

EXAMPLE 16(6)(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.13 (ethyl acetate:hexane=1:4); NMR (CDCl₃): δ 11.27 (br, 1H),7.19 (d, J=2.4 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.89 (dd, J=2.4, 8.1 Hz,1H), 5.57 (s, 1H), 2.75 (s, 2H), 2.28 (m, 1H), 1.92-1.18 (m, 16H).

EXAMPLE 17-EXAMPLE 17(1)

By the same procedure as described in example 9 using the compoundprepared in example 11(7) in place of the compound prepared in example1(68) and benzeneboronic acid or pyridin-3-ylboronic acid instead, thecompounds of the present invention were given.

EXAMPLE 17(Z)-2-(7-phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.88 (br, 1H),8.01 (d, J=2.0 Hz, 1H), 7.97-7.94 (m, 2H), 7.66-7.62 (m, 3H), 7.52-7.40(m, 6H), 7.30 (d, J=8.0 Hz, 1H), 6.39 (s, 1H), 2.95 (s, 2H), 1.40 (s,6H).

EXAMPLE 17(1)(Z)-2-(7-(pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-phenylethan-1-one

TLC: Rf0.32 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.87 (br, 1H),8.90 (d, J=1.5 Hz, 1H), 8.65 (dd, J=5.0, 1.5 Hz, 1H), 8.00-7.91 (m, 4H),7.64 (dd, J=8.0, 1.5 Hz, 1H), 7.46-7.41 (m, 4H), 7.35 (d, J=7.5 Hz, 1H),6.38 (s, 1H), 2.96 (s, 2H), 1.41 (s, 6H).

EXAMPLE 18(Z)-2-(6-(morpholin-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 12 (180 mg) in toluene(5 ml) were added morpholine (0.060 ml) and sodium t-butyrate (70.5 mg)and it was degassed and thereto was addeddichlorobis(tri-O-tolylphosphine)palladium(II) (12 mg) and the mixturewas stirred for 8 hours at 100° C. To the reaction mixture was addeddichlorobis(tri-O-tolylphosphine)palladium(II) (12 mg) and the mixturewas stirred for 2 hours. The mixture was allowed to cool and it wasdiluted with t-butyl methyl ether and it was washed with water and brinesuccessively, dried over anhydrous magnesium sulfate and concentrated.The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=4:1) to give the compound of the present invention(65 mg) having the following physical data.

TLC: Rf0.30 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (brs, 1H),7.98-7.90 (m, 2H), 7.73 (d, J=8.7 Hz, 1H), 7.45-7.39 (m, 3H), 6.81 (dd,J=8.7, 2.7 Hz, 1H), 6.65 (d, J=2.7 Hz, 1H), 6.24 (s, 1H), 3.88 (t, J=4.8Hz, 4H), 3.29 (t, J=4.8 Hz, 4H), 2.83 (s, 2H), 1.36 (s, 6H).

EXAMPLE 18(1)(Z)-2-(7-(morpholin-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

By the same procedure as described in example 18 using the compoundprepared in example 11(7) in place of the compound prepared in example12, the compound of the present invention having the following physicaldata was given.

TLC: Rf0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.87 (brs, 1H),7.97-7.90 (m, 2H), 7.48-7.41 (m, 3H), 7.32 (d, J=2.4 Hz, 1H), 7.12 (d,J=8.1 Hz, 1H), 7.00 (dd, J=8.1, 2.4 Hz, 1H), 6.25 (s, 1H), 3.91 (t,J=4.8 Hz, 4H), 3.21 (t, J=4.8 Hz, 4H), 2.82 (s, 2H), 1.35 (s, 6H).

EXAMPLE 19(Z)-2-(6-chloro-7-propoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

A solution of the compound prepared in example 11(153) (198 mg),dichloro bis(triphenylphosphine)palladium(II) (35 mg) and triethylamine(0.14 ml) in n-propanol (5 ml) was stirred overnight at 100° C. underatmosphere of carbon monooxide. To the reaction mixture were addeddichlorobis(triphenylphosphine)palladium(II) (315 mg) and triethylamine(0.84 ml) and the mixture was stirred overnight at 100° C. The reactionmixture was filtered over celite. The filtrate was added to water andthe mixture was extracted with ethyl acetate. The extract was washedwith a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:chloroform=3:2→2:3) togive the compound of the present invention (140 mg) having the followingphysical data.

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.22 (br, 1H),8.16 (s, 1H), 7.28 (s, 1H), 5.63 (s, 1H), 4.35 (t, J=6.5 Hz, 2H), 2.83(s, 2H), 2.32 (m, 1H), 1.90-1.20 (m, 12H), 1.29 (s, 6H), 1.07 (t, J=7.5Hz, 3H).

EXAMPLE 20(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylsulfinylphenyl)ethan-1-one

To a solution of the compound prepared in example 11(83) (296 mg) inacetone (4 ml) was added a suspension of Oxone (844 mg, product name) inwater/a saturated aqueous solution of sodium bicarbonate/acetone (2 ml/2ml/2 ml) and the mixture was stirred for 45 minutes at 0° C. To thereaction mixture was added water and was extracted with ethyl acetate.The extract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedcrudely by column chromatography on silica gel (hexane:ethylacetate=3:1→1:2) and then purified crudely by column chromatography onsilica gel (chloroform:methanol=100:0→100:1) and then washed witht-butyl methyl ether/hexane to give the compound of the presentinvention (20 mg) having the following physical data.

TLC: Rf0.07 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.91 (br, 1H),8.09 (d, J=8.5 Hz, 2H), 7.84 (d, J=7.5 Hz, 1H), 7.71 (d, J=8.5 Hz, 2H),7.46 (t, J=7.5 Hz, 1H), 7.36 (t, J=7.5 Hz, 1H), 7.23 (d, J=7.5 Hz, 1H),6.31 (s, 1H), 2.92 (s, 2H), 2.76 (s, 3H), 1.38 (s, 6H).

EXAMPLE 21(Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 1(68) (312 mg) inN-methylpyrrolidone (3 ml) was added copper cyanide (448 mg) at roomtemperature and the mixture was stirred for 19 hours at 180-190° C. Thereaction mixture was allowed to cool and thereto was added a saturatedaqueous solution of sodium bicarbonate and was extracted with ethylacetate. The extract was washed with water and brine successively, driedover anhydrous magnesium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (hexane:ethylacetate=20:1→15:1) to give the compound of the present invention (45 mg)having the following physical data.

TLC: Rf0.43 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.75 (br, 1H),7.95-7.91 (m, 3H), 7.64 (d, J=8.0 Hz, 1H), 7.53 (s, 1H), 7.49-7.41 (m,3H), 6.33 (br, 1H), 2.94 (s, 2H), 1.38 (s, 6H).

EXAMPLE 22(Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 11(7) (186 mg) inether (4 ml) was added n-butyl lithium (1.4 ml; 1.5M in hexane) dropwiseand the mixture was stirred for 90 minutes at 0° C. Thereto was addedacetone (0.23 ml) at 0° C. and the mixture was stirred for 45 minutes at0° C. To the reaction mixture was added water and the mixture wasextracted with ethyl acetate. The extract was washed with water andbrine successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified crudely by column chromatographyon silica gel (hexane:ethyl acetate=4:1→2.5:1) and then washed withethyl acetate to give the compound of the present invention (91 mg)having the following physical data.

TLC: Rf0.16 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.89 (br, 1H),7.98-7.94 (m, 3H), 7.53 (dd, J=8.0, 2.0 Hz, 1H), 7.47-7.42 (m, 3H), 7.19(d, J=8.0 Hz, 1H), 6.35 (s, 1H), 2.88 (s, 2H), 1.80 (br, 1H), 1.64 (s,6H), 1.36 (s, 6H).

EXAMPLE 22(1)-EXAMPLE 22(2)

By the same procedure as described in example 22 using the compoundprepared in example 11(188) or example 11(168) in place of the compoundprepared in example 11(7), the following compounds of the presentinvention were given.

EXAMPLE 22(1)(Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.36 (br, 1H),7.86 (d, J=2.0 Hz, 1H), 7.48 (dd, J=8.0, 2.0 Hz, 1H), 7.14 (d, J=8.0 Hz,1H), 5.66 (s, 1H), 2.82 (s, 2H), 2.32 (tt, J=11.5, 3.5 Hz, 1H),1.90-1.76 (m, 5H), 1.71-1.20 (m, 18H).

EXAMPLE 22(2)(Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.59 (br, 1H),7.87 (d, J=2.0 Hz, 1H), 7.47 (dd, J=8.0, 2.0 Hz, 1H), 7.14 (d, J=8.0 Hz,1H), 5.80 (s, 1H), 2.81 (s, 2H), 2.06 (br, 3H), 1.92 (br, 6H), 1.80 (s,1H), 1.75 (br, 6H), 1.63 (s, 6H), 1.29 (s, 6H).

EXAMPLE 23(Z)-2-(6-acetyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 12 (356 mg) in ether(10 ml) was added n-butyl lithium (1.6 ml, 1.6 M in hexane) dropwise at−78° C. and the mixture was stirred for 30 minutes at 0° C. and theretocarbon dioxide gas was bubbled. The reaction mixture was stirred for 20minutes at 0° C. and thereto was added methyl magnesium bromide (3.0 ml,0.9M in tetrahydrofuran) dropwise and the mixture was stirred for 2hours at 0° C. To the reaction mixture were added tetrahydrofuran, waterand ethyl acetate, and filtered and the filtrate was washed with asaturated aqueous solution of ammonium chloride and ethyl acetatesuccessively, and extracted with ethyl acetate. The combined organiclayer was washed with water and brine, dried over anhydrous magnesiumsulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=10:1→3:1) to give thecompound of the present invention (84 mg) having the following physicaldata.

TLC: Rf0.27 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.74 (br, 1H),7.97-7.93 (m, 2H), 7.91-7.88 (m, 2H), 7.80 (s, 1H), 7.48-7.42 (m, 3H),6.37 (s, 1H), 2.97 (s, 2H), 2.65 (s, 3H), 1.37 (s, 6H).

EXAMPLE 24(Z)-2-(7-hydroxyiminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 13(1) (209 mg) informic acid (4 ml) was added hydroxylamine hydrochloride (62 mg) and themixture was stirred for 1 hour at 100° C. The reaction mixture wasallowed to cool, and then it was added to a 2N aqueous solution ofsodium hydroxide and the mixture was extracted with ethyl acetate. Theextract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=3:1) togive the compound of the present invention (84 mg) having the followingphysical data.

TLC: Rf0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.83 (brs, 1H),8.20 (s, 1H), 8.03 (d, J=1.5 Hz, 1H), 7.98-7.93 (m, 2H), 7.64 (dd,J=8.1, 1.5 Hz, 1H), 7.48-7.43 (m, 3H), 7.41 (brs, 1H), 7.25 (d, J=8.1Hz, 1H), 6.35 (s, 1H), 2.92 (s, 2H), 1.37 (s, 6H).

EXAMPLE 24(1)-EXAMPLE 24(10)

By the same procedure as described in example 24 using the compoundprepared in example 13, example 13(8), example 13(10), example 13(9),example 13(11), example 13(13), example 13(12), example 13(15), example13(14) or example 13(16) in place of the compound prepared in example13(1), the following compounds of the present invention were given.

EXAMPLE 24(1)(Z)-2-(6-hydroxyiminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.51 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (brs, 1H),8.15 (s, 1H), 7.97-7.92 (m, 2H), 7.84 (d, J=8.1 Hz, 1H), 7.53 (dd,J=8.1, 1.5 Hz, 1H), 7.50-7.40 (m, 4H), 6.34 (s, 1H), 2.92 (s, 2H), 1.37(s, 6H).

EXAMPLE 24(2)(Z)-2-(7-hydroxyiminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.54 (br, 1H),8.49 (s, 1H), 8.08 (s, 1H), 7.55 (br, 1H), 6.68 (s, 1H), 5.75 (s, 1H),3.91 (s, 3H), 2.82 (s, 2H), 2.05 (br, 3H), 1.91 (br, 6H), 1.74 (br, 6H),1.30 (s, 6H).

EXAMPLE 24(3)(Z)-2-(7-hydroxyiminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.31 (br, 1H),8.49 (s, 1H), 8.08 (s, 1H), 7.38 (br, 1H), 6.68 (s, 1H), 5.61 (s, 1H),3.91 (s, 3H), 2.83 (s, 2H), 2.29 (m, 1H), 1.88-1.79 (m, 4H), 1.70-1.20(m, 12H).

EXAMPLE 24(4)(Z)-2-(7-hydroxyiminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.16 (hexane:ethyl acetate=4:1).

EXAMPLE 24(5)(Z)-2-(7-hydroxyiminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:1).

EXAMPLE 24(6)(Z)-2-(7-hydroxyiminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)—cyclohexylethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=2:1).

EXAMPLE 24(7)(Z)-2-(7-hydroxyiminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=3:1).

EXAMPLE 24(8)(Z)-2-(7-hydroxyiminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=2:1).

EXAMPLE 24(9)(Z)-2-(7-hydroxyiminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=3:1).

EXAMPLE 24(10)(Z)-2-(7-hydroxyiminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.22 (br, 1H),8.41 (s, 1H), 8.01 (s, 1H), 7.00 (s, 1H), 5.62 (s, 1H), 2.80 (s, 2H),2.50-2.44 (m, 4H), 1.96-1.42 (m, 12H), 1.28 (s, 6H).

EXAMPLE 25(Z)-2-(6-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-phenylethan-1-one

To the compound prepared in example 24(1) (360 mg) were added ethanol(16 ml) and a 50% aqueous solution of acetic acid (4 ml) and to themixture was added 10% palladium carbon (30 mg), and under atmosphere ofhydrogen the mixture was vigorously stirred for 7 hours. The reactionmixture was filtered over celite. The filtrate was concentrated andazeotroped with ethanol. The residue was purified by columnchromatography on silica gel (chloroform:methanol=19:1→4:1) to give thecompound of the present invention (240 mg) having the following physicaldata.

TLC: Rf0.22 (chloroform:methanol=4:1); NMR (CDCl₃): δ 11.82 (brs, 1H),7.97-7.91 (m, 2H), 7.79 (d, J=7.8 Hz, 1H), 7.46-7.40 (m, 3H), 7.28 (brd,J=7.8 Hz, 1H), 7.18 (brs, 1H), 6.32 (s, 1H), 3.93 (s, 2H), 2.89 (s, 2H),1.36 (s, 6H).

EXAMPLE 25(1)-EXAMPLE 25(10)

By the same procedure as described in example 25 using the compoundprepared in example 24, example 24(2) to example 24(5), example 24(7),example 24(6) or example 24(8)-example 24(10) in place of the compoundprepared in example 24(1), the following compounds of the presentinvention were given.

EXAMPLE 25(1)(Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.15 (hexane:ethyl acetate:isopropylamine=10:2:1); NMR (CDCl₃): δ11.86 (br, 1H), 7.98-7.94 (m, 2H), 7.77 (s, 1H), 7.46-7.38 (m, 4H), 7.19(d, J=7.5 Hz, 1H), 6.35 (s, 1H), 3.95 (s, 2H), 2.89 (s, 2H), 1.36 (s,6H).

EXAMPLE 25(2)(Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.16 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.52 (br, 1H),7.56 (s, 1H), 6.63 (s, 1H), 5.71 (s, 1H), 3.90 (s, 3H), 3.85 (s, 2H),2.80 (s, 2H), 2.06 (br, 3H), 1.92 (br, 6H), 1.75 (br, 6H), 1.29 (s, 6H).

EXAMPLE 25(3)(Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.10 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.31 (br, 1H),7.57 (s, 1H), 6.62 (s, 1H), 5.58 (s, 1H), 3.89 (s, 3H), 3.84 (s, 2H),2.81 (s, 2H), 2.29 (tt, J=11.5, 3.5 Hz, 1H), 1.90-1.79 (m, 4H),1.70-1.16 (m, 12H).

EXAMPLE 25(4)(Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.27 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.53 (brs, 1H),7.64 (s, 1H), 7.35 (brd, J=7.8 Hz, 1H), 7.14 (d, J=7.8 Hz, 1H), 5.79 (s,1H), 3.92 (s, 2H), 2.82 (s, 2H), 2.09-2.02 (m, 3H), 1.94-1.90 (m, 6H),1.77-1.72 (m, 6H), 1.29 (s, 6H).

EXAMPLE 25(5)(Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.25 (chloroform:methanol=10:1); NMR (CDCl₃) δ 11.23 (br, 1H),7.57 (s, 1H), 6.62 (s, 1H), 5.55 (s, 1H), 3.89 (s, 3H), 3.84 (s, 2H),2.80 (s, 2H), 2.45 (tt, J=10.0, 4.0 Hz, 1H), 1.95-1.88 (m, 2H),1.83-1.46 (m, 10H), 1.29 (s, 6H).

EXAMPLE 25(6)(Z)-2-(7-aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate:isopropylamine=10:1:0.5); NMR (CDCl₃):δ 11.52 (br, 1H), 7.63 (s, 1H), 6.96 (s, 1H), 5.78 (s, 1H), 3.90 (s,21), 2.78 (s, 2H), 2.37 (s, 3H), 2.06 (br, 3H), 1.93-1.92 (br, 6H),1.76-1.75 (br, 6H), 1.28 (s, 6H).

EXAMPLE 25(7)(Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.23 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.32 (brs, 1H),7.66 (brs, 1H), 7.34 (dd, J=7.8, 1.8 Hz, 1H), 7.14 (d, J=7.8 Hz, 1H),5.65 (s, 1H), 3.92 (s, 2H), 2.82 (s, 2H), 2.31 (tt, J=12.0, 3.3 Hz, 1H),1.93-1.18 (m, 16H).

EXAMPLE 25(8)(Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.28 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.24 (brs, 1H),7.66 (d, J=1.8 Hz, 1H), 7.34 (dd, J=7.8, 1.8 Hz, 1H), 7.14 (d, J=7.8 Hz,1H), 5.62 (s, 1H), 3.92 (s, 2H), 2.82 (s, 2H), 2.48 (tt, J=9.9, 3.3 Hz,1H), 1.97-1.43 (m, 12H), 1.28 (s, 6H).

EXAMPLE 25(9)(Z)-2-(7-aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.17 (hexane:ethyl acetate:isopropylamine=10:1:0.5); NMR (CDCl₃):δ 11.31 (br, 1H), 7.65 (s, 1H), 6.96 (s, 1H), 5.65 (s, 1H), 3.89 (s,2H), 2.78 (s, 2H), 2.36 (s, 3H), 2.30 (m, 1H), 1.86 (m, 4H), 1.68 (m,1H), 1.50-1.28 (m, 1H).

EXAMPLE 25(10)(Z)-2-(7-aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate:isopropylamine=10:1:1); NMR (CDCl₃): δ11.23 (br, 1H), 7.64 (s, 1H), 6.96 (s, 1H), 5.61 (s, 1H), 3.89 (s, 2H),2.78 (s, 2H), 2.46 (m, 1H), 2.36 (s, 3H), 1.96-1.46 (m, 12H), 1.28 (s,6H).

EXAMPLE 26(Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

To a solution of the compound prepared in example 24(4) (214 mg) inmethylene chloride (6 ml) were added trifluoromethanesulfonic anhydride(0.11 ml) and triethylamine (0.11 ml) and the mixture was stirred for 3hours at room temperature. To the reaction mixture was added a saturatedaqueous solution of sodium bicarbonate and the mixture was extractedwith ethyl acetate. The extract was washed with brine, dried overanhydrous magnesium sulfate and concentrated. The residue was crudelypurified by column chromatography on silica gel (hexane:ethylacetate=4:1), and it was dissolved in a mixture of ethanol (6 ml) andtetrahydrofuran (3 ml) and thereto was added sodium borohydride (75 mg)under cooling with ice and the mixture was stirred overnight. To thereaction mixture was added water and was extracted with methylenechloride. The extract was purified by column chromatography on silicagel (hexane:ethyl acetate=4:1) to give the compound of the presentinvention (52 mg) having the following physical data.

TLC: Rf0.23 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.36 (brs, 1H),8.00 (s, 1H), 7.65 (dd, J=7.8, 1.5 Hz, 1H), 7.30 (d, J=7.8 Hz, 1H), 5.76(s, 1H), 2.90 (s, 2H), 2.12-2.04 (m, 3H), 1.93-1.88 (m, 6H), 1.78-1.73(m, 6H), 1.30 (s, 6H).

EXAMPLE 26(1)-EXAMPLE 26(2)

By the same procedure as described in example 26 using the compoundprepared in example 24(6) or example 24(8) in place of the compoundprepared in example 24(4), the compounds of the present invention weregiven.

EXAMPLE 26(1)(Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.21 (brs, 1H),7.99 (d, J=1.5 Hz, 1H), 7.65 (dd, J=7.5, 1.5 Hz, 1H), 7.31 (d, J=7.5 Hz,1H), 5.62 (s, 1H), 2.90 (s, 2H), 2.33 (tt, J=11.4, 3.6 Hz, 1H),1.94-1.66 (m, 5H), 1.52-1.18 (m, 1H).

EXAMPLE 26(2)(Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1′-cycloheptylethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.12 (brs, 1H),7.98 (d, J=1.8 Hz, 1H), 7.65 (dd, J=8.1, 1.8 Hz, 1H), 7.30 (d, J=8.1 Hz,1H), 5.58 (s, 1H), 2.90 (s, 2H), 2.50 (tt, J=9.9, 3.9 Hz, 1H), 1.97-1.43(m, 12H), 1.30 (s, 6H).

EXAMPLE 27(Z)-2-(7-(morpholin-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(naphthalen-1-yl)ethan-1-one

To a solution of the compound prepared in example 13(2) (206 mg) intetrahydrofuran (5 ml) was added morpholine (0.065 ml) dropwise and themixture was stirred for 2 hours at room temperature. To the reactionmixture was added sodium triacetoxyborohydride (167 mg) and the mixturewas stirred for 3 hours. To the reaction mixture was added sodiumtriacetoxyborohydride (30 mg) and the mixture was stirred for 1 hour.The reaction mixture was added to a cold saturated aqueous solution ofsodium bicarbonate and the mixture was extracted with ethyl acetate. Theextract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=1:1→2:3) togive the compound of the present invention (250 mg) having the followingphysical data.

TLC: Rf0.17 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.80 (br, 1H),8.47 (m, 1H), 7.90-7.85 (m, 2H), 7.70 (dd, J=7.0, 1.0 Hz, 1H), 7.64 (s,1H), 7.55-7.45 (m, 3H), 7.40 (dd, J=8.0, 1.5 Hz, 1H), 7.17 (d, J=8.0 Hz,1H), 6.08 (s, 1H), 3.68 (t, J=7.5 Hz, 4H), 3.47 (s, 2H), 2.92 (s, 2H),2.41 (t, J=7.5 Hz, 4H), 1.41 (s, 6H).

EXAMPLE 27(1)-EXAMPLE 27(27)

By the same procedure as described in example 27 using the compoundprepared in example 13(1), example 13, example 13(1), example 13(8),example 13(9), example 13(11), example 11(119), example 13(12), example13(5), example 13(13), example 13(7), example 13(14), example 13(15),example 13(14), example 13(6) or example 13(16) and morpholine or acorresponding amine derivative instead, the compounds of the presentinvention were given.

EXAMPLE 27(1)(Z)-2-(7-(morpholin-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.32 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.87 (brs, 1H),7.99-7.93 (m, 2H), 7.75 (brs, 1H), 7.48-7.39 (m, 4H), 7.17 (d, J=7.8 Hz,1H), 6.33 (s, 1H), 3.74 (t, J=4.8 Hz, 4H), 3.55 (s, 2H), 2.88 (s, 2H),2.48 (t, J=4.8 Hz, 4H), 1.36 (s, 6H).

EXAMPLE 27(2)(Z)-2-(7-(piperidin-1-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.49 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.87 (brs, 1H),7.99-7.93 (m, 2H), 7.74 (brs, 1H), 7.48-7.39 (m, 4H), 7.16 (d, J=7.8 Hz,1H), 6.34 (s, 1H), 3.52 (s, 2H), 2.88 (s, 2H), 2.41 (brs, 4H), 1.60(quintet, J=5.4 Hz, 4H), 1.46 (m, 2H), 1.36 (s, 6H).

EXAMPLE 27(3)(Z)-2-(7-(N-methyl-N-(2-dimethylaminoethyl)aminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.13 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.87 (brs, 1H),7.99-7.93 (m, 2H), 7.76 (brs, 1H), 7.47-7.38 (m, 4H), 7.16 (d, J=7.8 Hz,1H), 6.34 (s, 1H), 3.57 (s, 2H), 2.88 (s, 2H), 2.55-2.44 (m, 4H), 2.28(s, 3H), 2.23 (s, 6H), 1.36 (s, 6H).

EXAMPLE 27(4)(Z)-2-(7-(N-(2-hydroxyethyl)-N-methylaminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.40 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.86 (brs, 1H),7.99-7.93 (m, 2H), 7.71 (brs, 1H), 7.47-7.38 (m, 4H), 7.18 (d, J=7.8 Hz,1H), 6.32 (s, 1H), 3.67 (t, J=5.4 Hz, 2H), 3.63 (s, 2H), 2.89 (s, 2H),2.64 (t, J=5.4 Hz, 2H), 2.42 (m, 1H), 2.28 (s, 3H), 1.36 (s, 6H).

EXAMPLE 27(5)(Z)-2-(7-(N-cyclohexylaminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.36 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.85 (brs, 1H),7.99-7.93 (m, 2H), 7.76 (brs, 1H), 7.47-7.38 (m, 4H), 7.17 (d, J=7.8 Hz,1H), 6.34 (s, 1H), 3.87 (s, 2H), 2.88 (s, 2H), 2.53 (m, 1H), 2.01-1.91(m, 2H), 1.82-1.71 (m, 2H), 1.62 (m, 1H), 1.38-1.08 (m, 6H), 1.36 (s,6H).

EXAMPLE 27(6)(Z)-2-(6-(morpholin-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.82 (brs, 1H),7.97-7.92 (m, 2H), 7.78 (d, J=8.4 Hz, 1H), 7.47-7.40 (m, 3H), 7.30 (brd,J=8.4 Hz, 1H), 7.19 (brs, 1H), 6.32 (s, 1H), 3.74 (t, J=4.8 Hz, 4H),3.53 (s, 2H), 2.89 (s, 2H), 2.48 (t, J=4.8 Hz, 4H), 1.36 (s, 6H).

EXAMPLE 27(7)(Z)-2-(6-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.31 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.82 (brs, 1H),7.98-7.92 (m, 2H), 7.78 (d, J=8.4 Hz, 1H), 7.47-7.40 (m, 3H), 7.27 (m,1H), 7.19 (brs, 1H), 6.32 (s, 1H), 3.46 (s, 2H), 2.89 (s, 2H), 2.28 (s,6H), 1.36 (s, 6H).

EXAMPLE 27(8)(Z)-2-(6-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.23 (chloroform:methanol=4:1); NMR (CDCl₃): δ 11.82 (brs, 1H),7.98-7.91 (m, 2H), 7.79 (d, J=8.4 Hz, 1H), 7.47-7.40 (m, 3H), 7.28 (m,1H), 7.20 (brs, 1H), 6.32 (s, 1H), 3.80 (s, 2H), 2.89 (s, 2H), 2.50 (s,3H), 1.36 (s, 6H).

EXAMPLE 27(9)(Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate:isopropylamine=10:2:1); NMR (CDCl₃): δ11.88 (br, 1H), 7.98-7.95 (m, 2H), 7.74 (d, J=1.5 Hz, 1H), 7.46-7.42 (m,3H), 7.39 (dd, J=8.0, 1.5 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 6.34 (s, 1H),3.47 (s, 2H), 2.89 (s, 2H), 2.28 (s, 6H), 1.36 (s, 6H).

EXAMPLE 27(10)(Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.22 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.58 (br, 1H),7.58 (s, 1H), 6.63 (s, 1H), 5.71 (s, 1H), 3.88 (s, 3H), 3.46 (s, 2H),2.80 (s, 2H), 2.30 (s, 6H), 2.06 (br, 3H), 1.92 (br, 6H), 1.74 (br, 6H),1.29 (s, 6H).

EXAMPLE 27(11)(Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate:isopropylamine=10:1:1); NMR (CDCl₃): δ11.53 (br, 1H), 7.56 (s, 1H), 6.63 (s, 1H), 5.71 (s, 1H), 3.88 (s, 3H),3.76 (s, 2H), 2.80 (s, 2H), 2.48 (s, 3H), 2.06 (br, 3H), 1.92 (br, 6H),1.75 (br, 6H), 1.29 (s, 6H).

EXAMPLE 27(12)(Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.54 (brs, 1H),7.64 (d, J=1.5 Hz, 1H), 7.36 (dd, J=7.5, 1.5 Hz, 1H), 7.13 (d, J=7.5 Hz,1H), 5.79 (s, 1H), 3.79 (s, 2H), 2.82 (s, 2H), 2.50 (s, 3H), 2.09-2.03(m, 3H), 1.94-1.90 (m, 6H), 1.77-1.72 (m, 6H), 1.28 (s, 6H).

EXAMPLE 27(13)(Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.24 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.57 (s, 1H), 6.62 (s, 1H), 5.54 (s, 1H), 3.88 (s, 3H), 3.75 (s, 2H),2.80 (s, 2H), 2.49-2.40 (m, 4H), 1.95-1.87 (m, 2H), 1.82-1.46 (m, 10H),1.29 (s, 6H).

EXAMPLE 27(14)(Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.16 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.52 (br, 1H),7.73 (s, 10H), 7.18 (s, 1H), 5.76 (s, 1H), 3.57 (s, 2H), 2.78 (s, 2H),2.34 (s, 6H), 2.05 (m, 3H), 1.91 (m, 6H), 1.74 (m, 6H), 1.28 (s, 6H).

EXAMPLE 27(15)(Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.18 (chloroform:methanol=50:1); NMR (CDCl₃): δ 11.53 (br, 10H),7.59 (s, 1H), 6.96 (s, 1H), 5.77 (s, 1H), 3.75 (s, 2H), 2.77 (s, 2H),2.55 (s, 3H), 2.38 (s, 3H), 2.06 (br, 3H), 1.93-1.92 (br, 6H), 1.76-1.75(br, 6H), 1.28 (s, 6H).

EXAMPLE 27(16)(Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.56 (br, 1H),7.53 (s, 1H), 6.96 (s, 1H), 5.75 (s, 1H), 3.41 (s, 2H), 2.77 (s, 2H),2.39 (s, 3H), 2.27 (s, 6H), 2.06 (br, 3H), 1.93-1.92 (br, 6H), 1.76-1.75(br, 6H), 1.28 (s, 6H).

EXAMPLE 27(17)(Z)-2-(6-chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.35 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.45(br, 1H), 7.79 (s, 1H), 7.20 (s, 1H), 5.81 (s, 1H), 3.94 (s, 2H), 2.79(s, 2H), 2.53 (s, 3H), 2.06 (m, 3H), 1.91 (m, 6H), 1.74 (m, 6H), 1.28(s, 6H).

EXAMPLE 27(18)(Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.21 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.31 (brs, 1H),7.67 (brs, 1H), 7.36 (dd, J=7.5, 1.5 Hz, 1H), 7.13 (d, J=7.5 Hz, 1H),5.66 (s, 1H), 3.79 (s, 2H), 2.82 (s, 2H), 2.49 (s, 3H), 2.31 (tt,J=11.4, 3.6 Hz, 1H), 1.94-1.64 (m, 5H), 1.54-1.18 (m, 11H).

EXAMPLE 27(19)(Z)-2-(6-chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.47 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.19(br, 1H), 7.71 (s, 1H), 7.19 (s, 1H), 5.59 (s, 1H), 3.87 (s, 2H), 2.79(s, 2H), 2.52 (s, 3H), 2.47 (m, 1H), 1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 27(20)(Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.24 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.24 (br, 1H),7.73 (s, 1H), 7.18 (s, 1H), 5.58 (s, 1H), 3.55 (s, 2H), 2.78 (s, 2H),2.48 (m, 1H), 2.33 (s, 6H), 1.95-1.40 (m, 12H), 1.28 (s, 6H).

EXAMPLE 27(21)(Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.20 (chloroform:methanol=20:1); NMR (CDCl₃): δ 11.31 (br, 1H),7:61 (s, 1H), 6.96 (s, 1H), 5.63 (s, 1H), 3.75 (s, 2H), 2.77 (s, 2H),2.54 (s, 3H), 2.37 (s, 3H), 2.34-2.26 (m, 1H), 1.90-1.79 (m, 4H), 1.71(m, 1H), 1.55-1.28 (m, 11H).

EXAMPLE 27(22)(Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.28 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.24 (brs, 1H),7.65 (d, J=1.8 Hz, 1H), 7.34 (dd, J=7.8, 1.8 Hz, 1H), 7.13 (d, J=7.8 Hz,1H), 5.62 (s, 1H), 3.78 (s, 2H), 2.82 (s, 2H), 2.49 (s, 3H), 2.47 (m,1H), 1.97-1.43 (m, 12H), 1.28 (s, 6H).

EXAMPLE 27(23)(Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.22 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.34 (br, 1H),7.55 (s, 1H), 6.95 (s, 1H), 5.62 (s, 1H), 3.39 (s, 2H), 2.77 (s, 2H),2.38 (s, 3H), 2.30 (m, 1H), 2.27 (s, 6H), 1.89-1.79 (m, 4H), 1.70 (m,1H), 1.54-1.28 (m, 1H).

EXAMPLE 27(24)(Z)-2-(6-chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.43 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.27(br, 1H), 7.71 (s, 1H), 7.19 (s, 1H), 5.62 (s, 1H), 3.87 (s, 2H), 2.79(s, 2H), 2.51 (s, 3H), 2.31 (m, 1H), 1.90-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 27(25)(Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.59 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.31(br, 1H), 7.74 (s, 1H), 7.18 (s, 1H), 5.62 (s, 1H), 3.55 (s, 2H), 2.79(s, 2H), 2.33 (s, 6H), 2.32 (m, 1H), 1.90-1.20 (m, 10H), 1.28 (s, 6H).

EXAMPLE 27(26)(Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.27 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.23 (br, 1H),7.61 (s, 1H), 6.96 (s, 1H), 5.60 (s, 1H), 3.75 (s, 2H), 2.77 (s, 2H),2.54 (s, 3H), 2.46 (m, 1H), 2.37 (s, 3H), 1.96-1.44 (m, 12H), 1.27 (s,6H).

EXAMPLE 27(27)(Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.27 (br, 1H),7.55 (s, 1H), 6.95 (s, 1H), 5.58 (s, 1H), 3.40 (s, 2H), 2.77 (s, 2H),2.48 (m, 1H), 2.38 (s, 3H), 2.27 (s, 6H), 1.96-1.44 (m, 12H), 1.28 (s,6H).

EXAMPLE 28(Z)-2-(6-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 13(85 ing) in methanol(4 ml) and tetrahydrofuran (1 ml) was added sodium borohydride (20 mg)and 10 minutes later thereto was added water and the mixture wasextracted with ethyl acetate. The extract was dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=3:1→1:1) to give thecompound of the present invention (90 mg) having the following physicaldata.

TLC: Rf0.34 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (br, 1H),7.96-7.93 (m, 2H), 7.82 (d, J=8.0 Hz, 1H), 7.46-7.41 (m, 3H), 7.32 (d,J=8.0 Hz, 1H), 7.23 (s, 1H), 6.33 (s, 1H), 4.76 (brd, 2H), 2.90 (s, 2H),1.86 (brt, 1H), 1.36 (s, 6H).

EXAMPLE 28(1)-EXAMPLE 28(13)

By the same procedure as described in example 28 using the compoundprepared in example 13, example 13(5)-example 13(16) in place of thecompound prepared in example 13, the following compounds of the presentinvention were given.

EXAMPLE 28(1)(Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.97-7.94 (m, 2H), 7.83 (s, 1H), 7.47-7.42 (m, 4H), 7.22 (d, J=7.5 Hz,1H), 6.35 (s, 1H), 4.77 (s, 2H), 2.90 (s, 2H), 1.80 (br, 1H), 1.36 (s,6H).

EXAMPLE 28(2)(Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.38 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.46 (br, 1H),7.83 (s, 1H), 7.20 (s, 1H), 5.78 (s, 1H), 4.83 (s, 2H), 2.82 (s, 2H),2.06 (m, 3H), 1.91 (m, 6H), 1.74 (m, 6H), 1.29 (s, 6H).

EXAMPLE 28(3)(Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.29 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.25 (br, 1H),7.84 (s, 1H), 7.19 (s, 1H), 5.65 (s, 1H), 4.82 (d, J=6.0 Hz, 2H), 2.80(s, 2H), 2.31 (m, 1H), 1.90-1.20 (m, 10H), 1.29 (s, 6H).

EXAMPLE 28(4)(Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.31 (ethyl acetate:hexane=1:3); NMR (CDCl₃): δ 11.16 (br, 1H),7.83 (s, 1H), 7.17 (s, 1H), 5.61 (s, 1H), 4.81 (s, 2H), 2.79 (s, 2H),2.46 (m, 1H), 1.95-1.40 (m, 12H), 1.27 (s, 6H).

EXAMPLE 28(5)(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.50 (br, 1H),7.64 (s, 1H), 6.65 (s, 1H), 5.72 (s, 1H), 4.72 (d, J=6.0 Hz, 2H), 3.92(s, 3H), 2.82 (s, 2H), 2.18 (t, J=6.0 Hz, 1H), 2.06 (br, 3H), 1.91 (br,6H), 1.75 (br, 6H), 1.29 (s, 6H).

EXAMPLE 28(6)(Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.51 (brs, 1H),7.71 (brs, 1H), 7.40 (dd, J=7.8, 1.8 Hz, 1H), 7.17 (d, J=7.8 Hz, 1H),5.80 (s, 1H), 4.75 (d, J=5.4 Hz, 2H), 2.83 (s, 2H), 2.09-2.03 (m, 3H),1.94-1.90 (m, 6H), 1.78-1.72 (m, 6H), 1.29 (s, 6H).

EXAMPLE 28(7)(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.10 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.29 (br, 1H),7.64 (s, 1H), 6.65 (s, 1H), 5.58 (s, 1H), 4.71 (d, J=6.0 Hz, 2H), 3.91(s, 3H), 2.82 (s, 2), 2.29 (tt, J=11.5, 3.5 Hz, 1H), 2.16 (t, J=6.0 Hz,1H), 1.89-1.78 (m, 4H), 1.69 (m, 1H), 1.56-1.20 (m, 1H).

EXAMPLE 28(8)(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.21 (br, 1H),7.64 (s, 1H), 6.65 (s, 1H), 5.55 (s, 1H), 4.71 (d, J=6.5 Hz, 2H), 3.91(s, 3H), 2.82 (s, 2H), 2.45 (m, 1H), 2.16 (t, J=6.5 Hz, 1H), 1.95-1.88(m, 2H), 1.82-1.46 (m, 10H), 1.29 (s, 6H).

EXAMPLE 28(9)(Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.17 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.50 (br, 10H),7.69 (s, 1H), 6.99 (s, 1H), 5.78 (s, 1H), 4.75 (d, J=5.7 Hz, 2H), 2.79(s, 2H), 2.39 (s, 3H), 2.06 (br, 3H), 1.92-1.91 (br, 6H), 1.76-1.75 (br,6H), 1.28 (s, 6H).

EXAMPLE 28(10)(Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.30 (brs, 1H),7.72 (brs, 1H), 7.39 (dd, J=7.8, 1.8 Hz, 1H), 7.17 (d, J=7.8 Hz, 1H),5.66 (s, 1H), 4.74 (s, 2H), 2.83 (s, 2H), 2.30 (tt, J=11.4, 3.6 Hz, 1H),1.93-1.18 (m, 16H).

EXAMPLE 28(11)(Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.29 (br, 10H),7.70 (s, 1H), 6.98 (s, 1H), 5.64 (s, 1H), 4.74 (d, J=5.1 Hz, 2H), 2.79(s, 2H), 2.37 (s, 3H), 2.30 (m, 1H), 1.92-1.76 (m, 4H), 1.69 (m, 1H),1.55-1.28 (m, 1H).

EXAMPLE 28(12)(Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.22 (brs, 1H),7.71 (brs, 1H), 7.39 (dd, J=7.8, 1.8 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H),5.62 (s, 1H), 4.74 (s, 2H), 2.83 (s, 2H), 2.46 (tt, J=9.9, 3.3 Hz, 1H),1.99-1.42 (m, 12H), 1.28 (s, 6H).

EXAMPLE 28(13)(Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.21 (br, 1H),7.70 (s, 1H), 6.98 (s, 1H), 5.61 (s, 1H), 4.74 (d, J=4.8 Hz, 2H), 2.79(s, 2H), 2.46 (m, 1H), 2.37 (s, 3H), 1.96-1.86 (m, 2H), 1.84-1.56 (m,10H), 1.28 (s, 6H).

EXAMPLE 29-EXAMPLE 29(11)

By the same procedure as described in example 8 using the compoundprepared in example 2(3) or example 14, example 14(2), example 14(3),example 14(10), example 14(3) or example 14(10), and acetyl chloride ora corresponding halide derivative, the following compounds of thepresent invention were given.

EXAMPLE 29(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-phenylsulfonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.29 (br, 1H),7.81-7.77 (m, 2H), 7.64-7.51 (m, 4H), 7.40 (t, J=7.5 Hz, 1H), 7.31-7.26(m, 1H), 7.17 (d, J=7.5 Hz, 1H), 5.54 (s, 1H), 3.88-3.85 (m, 2H), 2.84(s, 2H), 2.41-2.33 (m, 2H), 2.24-2.14 (m, 1H), 1.97-1.76 (m, 4H), 1.29(s, 6H).

EXAMPLE 29(1)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-ethylsulfonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.32 (br, 1H),7.69 (d, J=7.5 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H),7.19 (d, J=7.5 Hz, 1H), 5.62 (s, 1H), 3.88-3.84 (m, 2H), 3.01-2.86 (m,6H), 2.46-2.35 (m, 1H), 1.99-1.93 (m, 2H), 1.89-1.78 (m, 2H), 1.38 (t,J=7.0 Hz, 3H), 1.31 (s, 6H).

EXAMPLE 29(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-propylsulfonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.32 (br, 1H),7.69 (d, J=7.5 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H),7.19 (d, J=7.5 Hz, 1H), 5.62 (s, 1H), 3.87-3.83 (m, 2H), 2.93-2.83 (m,6H), 2.44-2.35 (m, 1H), 1.99-1.75 (m, 6H), 1.31 (s, 6H), 1.06 (t, J=7.5Hz, 3H).

EXAMPLE 29(3)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-butylsulfonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.10 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.33 (br, 1H),7.69 (dd, J=7.5, 1.0 Hz, 1H), 7.41 (dt, J=1.0, 7.5 Hz, 1H), 7.30 (dt,J=1.0, 7.5 Hz, 1H), 7.19 (dd, J=7.5, 1.0 Hz, 1H), 5.62 (s, 1H),3.87-3.83 (m, 2H), 2.95-2.83 (m, 6H), 2.45-2.34 (m, 1H), 2.00-1.93 (m,2H), 1.90-1.76 (m, 4H), 1.51-1.40 (m, 2H), 1.31 (s, 6H), 0.96 (t, J=7.5Hz, 3H).

EXAMPLE 29(4)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-octyldulfonylpiperidin-4-yl)ethan-1-one

TLC: Rf0.22 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.33 (br, 1H),7.69 (d, J=7.5 Hz, 1H), 7.41 (t, J=7.5 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H),7.19 (d, J=7.5 Hz, 1H), 5.61 (s, 1H), 3.87-3.83 (m, 2H), 2.94-2.82 (m,6H), 2.44-2.34 (m, 1H), 1.98-1.93 (m, 2H), 1.87-1.76 (m, 4H), 1.44-1.22(m, 16H), 0.88 (brt, 3H).

EXAMPLE 29(5)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-acetylaminophenyl)ethan-1-one

TLC: Rf0.09 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.80 (br, 1H),7.94 (d, J=8.5 Hz, 2H), 7.83 (d, J=7.5 Hz, 1H), 7.58 (d, J=8.5 Hz, 2H),7.43 (t, J=7.5 Hz, 1H), 7.37-7.32 (m, 2H), 7.21 (d, J=7.5 Hz, 1H), 6.31(s, 1H), 2.90 (s, 2H), 2.21 (s, 3H), 1.36 (s, 6H).

EXAMPLE 29(6)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-acetylaminophenyl)ethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.87-7.82 (m, 3H), 7.69 (d, J=8.0 Hz, 1H), 7.46-7.32 (m, 4H), 7.22 (d,J=7.5 Hz, 1H), 6.31 (s, 1H), 2.91 (s, 2H), 2.21 (s, 3H), 1.37 (s, 6H).

EXAMPLE 29(7)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-mesylaminophenyl)ethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.86 (br, 1H),7.82 (d, J=7.5 Hz, 1H), 7.78-7.73 (m, 2H), 7.48-7.40 (m, 3H), 7.36 (t,J=7.5 Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 6.54 (br, 1H), 6.29 (s, 1H), 3.02(s, 3H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 29(8)(Z)-2-(7-acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.23 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (br, 1H),7.96-7.91 (m, 3H), 7.64 (dd, J=8.0, 2.0 Hz, 1H), 7.45-7.39 (m, 4H), 7.17(d, J=8.0 Hz, 1H), 6.29 (s, 1H), 2.84 (s, 2H), 2.23 (s, 3H), 1.33 (s,6H).

EXAMPLE 29(9)(Z)-2-(7-acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.48 (br, 1H),7.78 (d, J=2.0 Hz, 1H), 7.62 (dd, J=8.0, 2.0 Hz, 1H), 7.27 (br, 1H),7.13 (d, J=8.0 Hz, 1H), 5.74 (s, 1H), 2.79 (s, 2H), 2.22 (s, 3H), 2.05(br, 3H), 1.91 (br, 6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 29(10)(Z)-2-(7-mesylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.14 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.80 (br, 1H),7.96-7.92 (m, 2H), 7.64 (d, J=2.0 Hz, 1H), 7.47-7.42 (m, 3H), 7.35 (dd,J=8.0, 2.0 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 6.54 (br, 1H), 6.27 (s, 1H),3.06 (s, 3H), 2.88 (s, 2H), 1.36 (s, 6H).

EXAMPLE 29(11)(Z)-2-(7-mesylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.46 (br, 1H),7.51 (d, J=2.0 Hz, 1H), 7.34 (dd, J=8.0, 2.0 Hz, 1H), 7.18 (d, J=8.0 Hz,1H), 6.46 (br, 1H), 5.72 (s, 1H), 3.05 (s, 3H), 2.81 (s, 2H), 2.06 (br,3H), 1.90 (br, 6H), 1.74 (br, 6H), 1.29 (s, 6H).

EXAMPLE 30(Z)-2-(6-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 15 (100 mg) intetrahydrofuran (3 ml) were added triethylamine (0.09 ml) and isobutylchlorocarbonate (0.08 ml) under cooling with ice and the mixture wasstirred for 30 minutes at room temperature. The precipitate was removed.The filtrate was added to a solution of a 40% aqueous solution ofmethylamine (0.120 ml) in tetrahydrofuran (2 ml) under cooling with iceand the mixture was stirred overnight at room temperature. The reactionmixture was concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=1:1) to give thecompound of the present invention (92 mg) having the following physicaldata.

TLC: Rf0.46 (ethyl acetate); NMR (CDCl₃): δ 11.76 (brs, 1H), 7.97-7.92(m, 2H), 7.87 (d, J=9.0 Hz, 1H), 7.69-7.63 (m, 2H), 7.48-7.42 (m, 3H),6.34 (s, 1H), 6.20 (brs, 1H), 3.05 (d, J=4.8 Hz, 3H), 2.94 (s, 2H), 1.36(s, 6H).

EXAMPLE 30(1)-EXAMPLE 30(11)

By the same procedure as described in example 30 using the compoundprepared in example 15 or example 15(1)-example 15(4) or example 15(13)and methylamine or a corresponding amine derivative, the followingcompounds of the present invention were given.

EXAMPLE 30(1)(Z)-2-(6-dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.40 (ethyl acetate); NMR (CDCl₃): δ 11.78 (brs, 1H), 7.97-7.92(m, 2H), 7.86 (d, J=8.1 Hz, 1H), 7.48-7.41 (m, 3H), 7.37 (dd, J=8.1, 1.5Hz, 1H), 7.29 (d, J=1.5 Hz, 1H), 6.34 (s, 1H), 3.14 (s, 3H), 3.01 (s,3H), 2.92 (s, 2H), 1.37 (s, 6H).

EXAMPLE 30(2)(Z)-2-(6-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-phenylethan-1-one

TLC: Rf0.36 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.76 (brs, 1H),7.98-7.88 (m, 3H), 7.75-7.69 (m, 2H), 7.49-7.41 (m, 3H), 6.35 (s, 1H),6.12 (brs, 1H), 5.71 (brs, 1H), 2.95 (s, 2H), 1.37 (s, 6H).

EXAMPLE 30(3)(Z)-2-(7-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-phenylethan-1-one

TLC: Rf0.07 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.82 (br, 1H),8.31 (d, J=1.5 Hz, 1H), 7.98-7.94 (m, 2H), 7.83 (dd, J=8.0, 1.5 Hz, 1H),7.48-7.42 (m, 3H), 7.31 (d, J=8.0 Hz, 1H), 6.39 (s, 1H), 6.10 (br, 1H),5.67 (br, 1H), 2.95 (s, 2H), 1.37 (s, 6H).

EXAMPLE 30(4)(Z)-2-(7-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.14 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (br, 1H),8.24 (d, J=2.0 Hz, 1H), 7.98-7.94 (m, 2H), 7.78 (dd, J=8.0, 2.0 Hz, 1H),7.48-7.41 (m, 3H), 7.28 (d, J=8.0 Hz, 1H), 6.39 (s, 1H), 6.20 (br, 1H),3.07 (d, J=5.0 Hz, 3H), 2.94 (s, 2H), 1.36 (s, 6H).

EXAMPLE 30(5)(Z)-2-(7-dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.79 (br, 1H),7.96-7.91 (m, 3H), 7.49-7.40 (m, 4H), 7.26 (m, 1H), 6.33 (s, 1H), 3.16(br, 3H), 3.04 (br, 3H), 2.93 (s, 2H), 1.37 (s, 6H).

EXAMPLE 30(6)(Z)-2-(7-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.34 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.51 (br, 1H),8.19 (d, J=1.2 Hz, 1H), 7.77 (dd, J=1.2, 7.5 Hz, 1H), 7.27 (d, J=7.5 Hz,1H), 5.84 (s, 1H), 2.89 (s, 2H), 2.06 (br, 3H), 1.92-1.91 (br, 6H),1.76-1.75 (br, 6H), 1.30 (s, 6H).

EXAMPLE 30(7)(Z)-2-(7-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.49 (br, 1H),8.14 (d, J=1.2 Hz, 1H), 7.70 (dd, J=1.2, 7.8 Hz, 1H), 7.23 (d, J=7.8 Hz,1H), 6.14 (br, 1H), 5.84 (s, 1H), 3.06 (d, J=7.8 Hz, 3H), 2.87 (s, 2H),2.06 (br, 3H), 1.92-1.91 (b r, 6H), 1.75 (s, 6H), 1.29 (s, 6H).

EXAMPLE 30(8)(Z)-2-(7-dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.50 (chloroform:methanol=50:1); NMR (CDCl₃): δ 11.45 (br, 1H),7.81 (d, J=1.2 Hz, 1H), 7.41 (dd, J=1.2, 7.8 Hz, 1H), 7.20 (d, J=7.8 Hz,1H), 5.78 (s, 1H), 3.15 (br, 3H), 3.02 (br, 3H), 2.86 (s, 2H), 2.05 (br,3H), 1.90-1.89 (br, 6H), 1.74 (br, 6H), 1.30 (s, 6H).

EXAMPLE 30(9)(Z)-2-(6-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.78 (d, J=8.0 Hz, 1H), 7.70-7.66 (m, 2H), 6.14 (br, 1H), 5.83 (br, 1H),5.66 (s, 1H), 2.89 (s, 2H), 2.30 (tt, J=11.5, 3.5 Hz, 1H), 1.90-1.80 (m,4H), 1.70 (m, 1H), 1.50-1.20 (m, 1H).

EXAMPLE 30(10)(Z)-2-(6-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.15 (br, 1H),7.78 (d, J=8.0 Hz, 1H), 7.69-7.66 (m, 2H), 6.08 (br, 1H), 5.75 (br, 1H),5.63 (s, 1H), 2.89 (s, 2H), 2.48 (tt, J=10.0, 4.0 Hz, 1H), 1.95-1.88 (m,2H), 1.82-1.45 (m, 10H), 1.29 (s, 6H).

EXAMPLE 30(11)(Z)-2-(6-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.13 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.40 (br, 1H),7.79 (d, J=8.0 Hz, 1H), 7.70-7.66 (m, 2H), 6.05 (br, 1H), 5.81 (s, 1H),5.76 (br, 1H), 2.89 (s, 2H), 2.06 (br, 3H), 1.91 (br, 6H), 1.75 (br,6H), 1.30 (s, 6H).

EXAMPLE 31(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyano-2-methoxyphenyl)ethan-1-one

To a suspension of the compound prepared in example 13(4) (423 mg) informic acid (10 ml) was added hydroxylamine chloride (1.05 g) and themixture was stirred for 30 minutes at 130° C. The reaction mixture wasallowed to cool and thereto were added ice and water, and theprecipitate was collected and was dissolved in ethyl acetate, washedwith water and a saturated aqueous solution of sodium chloridesuccessively, dried over anhydrous magnesium sulfate and concentrated.The residue was crudely purified by column chromatography on silica gel(hexane:ethyl acetate=5:1→2:1) and then washed with t-butyl methyl etherto give the compound of the present invention (65 mg) having thefollowing physical data.

TLC: Rf0.32 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.73 (br, 1H),7.73-7.70 (m, 2H), 7.44 (dt, J=1.0, 7.5 Hz, 1H), 7.34-7.29 (m, 2H),7.23-7.19 (m, 2H), 6.16 (s, 1H), 3.94 (s, 3H), 2.91 (s, 2H), 1.37 (s,6H).

EXAMPLE 31(1)-EXAMPLE 31(3)

By the same procedure as described in example 31 using the compoundprepared in example 13(1), example 13(12) or example 13(14) in place ofthe compound prepared in 13(4), the following compounds of the presentinvention were given.

EXAMPLE 31(1)(Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.73 (brs, 1H),8.11 (d, J=1.5 Hz, 1H), 7.99-7.93 (m, 2H), 7.70 (dd, J=8.1, 1.5 Hz, 1H),7.51-7.44 (m, 3H), 7.35 (d, J=8.1 Hz, 1H), 6.31 (s, 1H), 2.97 (s, 2H),1.37 (s, 6H).

EXAMPLE 31(2)(Z)-2-(7-cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.50 (methylene chloride); NMR (CDCl₃): δ 11.37 (br, 1H), 7.94(s, 1H), 7.14 (s, 1H), 5.73 (s, 1H), 2.84 (s, 2H), 2.57 (s, 3H), 2.07(br, 3H), 1.91-1.90 (br, 6H), 1.76 (br, 6H), 1.29 (s, 6H).

EXAMPLE 31(3)(Z)-2-(7-cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.45 (methylene chloride); NMR (CDCl₃): δ 11.21 (br, 1H), 7.92(s, 1H), 7.14 (s, 1H), 5.58 (s, 1H), 2.84 (s, 2H), 2.57 (s, 3H),2.36-2.28 (m, 1H), 1.92-1.29 (m, 16H).

EXAMPLE 32(Z)-2-(6-ethynyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a suspension of (bromomethyl)triphenylphosphonium bromide (371 mg) intetrahydrofuran (3 ml) was added -potassium t-butoxide (2.55 ml, 1.0M inTHF) at −78° C. and the mixture was stirred for 30 minutes at 0° C. Tothe mixture was added a solution of the compound prepared in example 13(200 mg) in tetrahydrofuran (5 ml) dropwise and the mixture was stirredfor 90 minutes at 0° C. and for 60 minute at room temperature. To thereaction mixture was added ice-water and the mixture was extracted withethyl acetate. The extract was washed with water and a saturated aqueoussolution of sodium chloride successively, dried over anhydrous magnesiumsulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=20:1→10:1) to givethe compound of the present invention (127 mg) having the followingphysical data.

TLC: Rf0.46 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.76 (br, 1H),7.96-7.92 (m, 2H), 7.78 (d, J=8.0 Hz, 1H), 7.47-7.41 (m, 4H), 7.35 (d,J=1.0 Hz, 1H), 6.31 (s, 1H), 3.22 (s, 1H), 2.88 (s, 2H), 1.36 (s, 6H).

EXAMPLE 32(1)-EXAMPLE 32(2)

By the same procedure as described in example 32 using the compoundprepared in example 13(1) or example 13(3) in place of the compoundprepared in example 13, the following compounds of the present inventionwere given.

EXAMPLE 32(1)(Z)-2-(7-ethynyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.79 (br, 1H),7.97-7.94 (m, 3H), 7.54 (dd, J=8.0, 1.5 Hz, 1H), 7.47-7.42 (m, 3H), 7.19(d, J=8.0 Hz, 1H), 6.31 (s, 1H), 3.14 (s, 1H), 2.90 (s, 2H), 1.36 (s,6H).

EXAMPLE 32(2)(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-ethynylphenyl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=3:1); NMR(CDCl₃): δ 11.88 (br, 1H),7.91 (d, J=8.5 Hz, 2H), 7.82 (d, J=7.5 Hz, 1H), 7.55 (d, J=8.5 Hz, 2H),7.44 (t, J=7.5 Hz, 1H), 7.35 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H),6.31 (s, 1H), 3.17 (s, 1H), 2.91 (s, 2H), 1.37 (s, 6H).

EXAMPLE 33(Z)-2-(6-((E)-2-carboxyethenyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 13 (200 mg) inpyridine (5 ml) was added piperidine (2 drops) at room temperature andthen thereto was added malonic acid (122 mg) and the mixture was stirredfor 20 minutes at room temperature, for 30 minutes at 85° C. and for 3.5hours at 100° C. and overnight at 80° C. The reaction mixture wasallowed to cool and was extracted with ethyl acetate. The organic layerwas washed with a saturated aqueous solution of ammonium chloride, waterand brine successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=2:1→ethyl acetate) to give the compoundof the present invention (173 mg) having the following physical data.

TLC: Rf0.16 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.76 (br, 1H),7.97-7.93 (m, 2H), 7.87 (d, J=8.0 Hz, 1H), 7.78 (d, J=16.0 Hz, 1H), 7.52(dd, J=8.0, 1.5 Hz, 1H), 7.48-7.41 (m, 3H), 7.40 (d, J=1.5 Hz, 1H), 6.54(d, J=16.0 Hz, 1H), 6.35 (s, 1H), 2.93 (s, 2H), 1.38 (s, 6H).

EXAMPLE 34(Z)-2-(6-((E)-2-methoxycarbonylethenyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 33 (90 mg) indimethylformamide (2 ml) was added potassium carbonate (30 mg) at roomtemperature and thereto was added methyl iodide (0.033 ml) and themixture was stirred overnight at room temperature. To the reactionmixture was added water and the precipitate was collected. It wasdissolved in ethyl acetate and the mixture was washed with water andbrine, dried over anhydrous magnesium sulfate and concentrated to givethe compound of the present invention (94 mg) having the followingphysical data.

TLC: Rf0.68 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.76 (br, 1H),7.96-7.93 (m, 2H), 7.85 (d, J=8.0 Hz, 1H), 7.69 (d, J=16.0 Hz, 1H),7.51-7.41 (m, 4H), 7.36 (s, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.34 (s, 1H),3.83 (s, 3H), 2.92 (s, 2H), 1.38 (s, 6H).

EXAMPLE 34(1)-EXAMPLE 34(2)

By the same procedure as described in example 34 using the compoundprepared in example 15 or example 15(1) in place of the compoundprepared in example 33, the following compounds of the present inventionwere given.

EXAMPLE 34(1)(Z)-2-(6-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.43 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.75 (br, 1H),8.01-7.94 (m, 3H), 7.90-7.88 (m, 2H), 7.48-7.41 (m, 3H), 6.37 (s, 1H),3.96 (s, 3H), 2.95 (s, 2H), 1.37 (s, 6H).

EXAMPLE 34(2)(Z)-2-(7-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.25 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.83 (br, 1H),8.49 (d, J=2.0 Hz, 1H), 8.10 (dd, J=8.0, 2.0 Hz, 1H), 7.99-7.96 (m, 2H),7.49-7.44 (m, 3H), 7.31 (d, J=8.0 Hz, 1H), 6.40 (s, 1H), 3.98 (s, 3H),2.96 (s, 2H), 1.37 (s, 6H).

EXAMPLE 35(Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

To a solution of the compound prepared in example 19 (58 mg) intetrahydrofuran (1 ml) and methanol (1 ml) was added a 2N aqueoussolution of sodium hydroxide and the mixture was stirred overnight atroom temperature. The reaction mixture was neutralized with 1Nhydrochloric acid and the mixture was extracted with ethyl acetate. Theextract was washed with brine, dried over anhydrous magnesium sulfateand concentrated. The residue was washed with a mixture of hexane andethyl acetate to give the compound of the present invention (45 mg)having the following physical data.

TLC: Rf0.40 (water:methanol:chloroform=1:10:100); NMR (CDCl₃): δ 11.24(br, 1H), 8.35 (s, 1H), 7.33 (s, 1H), 5.66 (s, 1H), 2.86 (s, 2H), 2.34(m, 1H), 1.95-1.65 (m, 5H), 1.55-1.20 (m, 5H), 1.31 (s, 6H).

EXAMPLE 35(1)-EXAMPLE 35(2)

By the same procedure as described in example 35 using the compoundprepared in example 11(197) or example 11(198) in place of the compoundprepared in example 19, the following compounds of the present inventionwere given.

EXAMPLE 35(1)(Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.44 (brs, 1H),8.33 (s, 1H), 7.33 (s, 1H), 5.80 (s, 1H), 2.86 (s, 2H), 2.10-2.03 (m,3H), 1.93-1.89 (m, 6H), 1.77-1.72 (m, 6H), 1.31 (s, 6H).

EXAMPLE 35(2)(Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.16 (brs, 1H),8.34 (s, 1H), 7.32 (s, 1H), 5.63 (s, 1H), 2.85 (s, 2H), 2.50 (tt, J=9.9,3.9 Hz, 1H), 1.97-1.42 (m, 12H), 1.31 (s, 6H).

EXAMPLE 36(Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

By the same procedure as described in example 3 using1,3,3,4,4-pentamethyl-3,4-dihydroisoquinoline in place of the compoundprepared in reference example 2, and 4-cyanobenzoyl chloride in place of3-cyanobenzoyl chloride, the present invention having the followingphysical data was given.

TLC: Rf0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.90 (br, 1H),8.03 (d, J=8.5 Hz, 2H), 7.79 (dd, J=7.5, 1.0 Hz, 1H), 7.72 (d, J=8.5 Hz,2H), 7.52 (dt, J=1.0, 7.5 Hz, 1H), 7.45 (dd, J=7.5, 1.0 Hz, 1H), 7.34(dt, J=1.0, 7.5 Hz, 1H), 6.25 (s, 1H), 1.31 (br, 12H).

EXAMPLE 37(Z)-2-(7-formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a mixture of acetic anhydride (0.50 ml) and formic acid (5 ml) wasadded the compound prepared in example 14(3) (151 mg) and the mixturewas stirred for 1 hour at 70° C. The reaction mixture was allowed tocool and to the mixture was added ice and it was neutralized with asaturated aqueous solution of sodium bicarbonate and it was extractedwith ethyl acetate. The extract was washed with a saturated aqueoussolution of sodium bicarbonate, water and brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=2:1) to give thecompound of the present invention (131 mg) having the following physicaldata.

TLC: Rf0.21 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 11.74 (brs,1H), 10.26 (brs, 1H), 8.13 (d, J=1.8 Hz, 1H), 7.89-7.84 (m, 2H), 7.74(dd, J=8.1, 1.8 Hz, 1H), 7.50-7.43 (m, 3H), 7.28 (d, J=8.1 Hz, 1H), 7.26(s, 1H), 6.24 (s, 1H), 2.87 (s, 2H), 1.27 (s, 6H).

EXAMPLE 37(1)(Z)-2-(6-formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

By the same procedure as described in example 37 using the compoundprepared in example 40 in place of the compound prepared in example14(3), the compound of the present invention having the followingphysical data was given.

TLC: Rf0.40 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.79 (brs, 1H),8.43 (s, 1H), 7.97-7.92 (m, 2H), 7.80 (d, J=8.4 Hz, 1H), 7.63 (d, J=2.1Hz, 1H), 7.47-7.39 (m, 3H), 7.37 (dd, J=8.4, 2.1 Hz, 1H), 6.27 (s, 1H),2.89 (s, 2H), 1.36 (s, 6H).

EXAMPLE 38 (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a suspension of lithium aluminum hydride (77 mg) in tetrahydrofuran(1 ml) was added the compound prepared in example 37 (131 mg) intetrahydrofuran (4 ml) and the mixture was stirred for 4 hours at roomtemperature. To the reaction mixture was added a saturated aqueoussolution of sodium sulfate and the mixture was filtered over celite. Thefiltrate was concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=4:1) to give thecompound of the present invention (73 mg) having the following physicaldata.

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.85 (brs, 1H),7.97-7.91 (m, 2H), 7.46-7.40 (m, 3H), 7.03 (d, J=8.1 Hz, 1H), 7.03 (d,J=2.4 Hz, 1H), 6.71 (dd, J=8.1, 2.4 Hz, 1H), 6.25 (s, 1H), 2.91 (s, 3H),2.78 (s, 2H), 1.35 (s, 6H).

EXAMPLE 38(1)-EXAMPLE 38(2)

By the same procedure as described in example 38 using the compoundprepared in example 37(1) or example 30(4) in place of the compoundprepared in example 37, the following compounds of the present inventionwere given.

EXAMPLE 38(1)(Z)-2-(6-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.69 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.85 (brs, 1H),7.97-7.91 (m, 2H), 7.66 (d, J=8.7 Hz, 1H), 7.44-7.38 (m, 3H), 6.51 (dd,J=8.7, 2.4 Hz, 1H), 6.35 (d, J=2.4 Hz, 1H), 6.21 (s, 1H), 4.14 (brs,1H), 2.91 (s, 3H), 2.80 (s, 2H), 1.36 (s, 6H).

EXAMPLE 38(2)(Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate:isopropylamine=10:2:1); NMR (CDCl₃): δ11.86 (br, 1H), 7.98-7.95 (m, 2H), 7.77 (s, 1H), 7.47-7.37 (m, 4H), 7.18(d, J=8.0 Hz, 1H), 6.35 (s, 1H), 3.81 (s, 2H), 2.89 (s, 2H), 2.50 (s,3H), 1.36 (s, 6H).

EXAMPLE 39(Z)-2-(6-t-butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a suspension of the compound prepared in example 15 (965 mg) int-butanol (15 ml) were added triethylamine (0.460 ml) anddiphenylphosphorylazide (0.710 ml) and the mixture was stirred for 3hours at 100° C. The reaction mixture was allowed to cool and dilutedwith ethyl acetate and the mixture was washed with water, a saturatedaqueous solution of sodium bicarbonate and brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=9:1) to give thecompound of the present invention (1.04 g) having the following physicaldata.

TLC: Rf0.58 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (brs, 1H),7.96-7.91 (m, 2H), 7.74 (d, J=8.7 Hz, 1H), 7.46-7.40 (m, 4H), 7.16 (dd,J=8.7, 2.7 Hz, 1H), 6.64 (brs, 1H), 6.26 (s, 1H), 2.87 (s, 2H), 1.54 (s,9H), 1.35 (s, 6H).

EXAMPLE 39(1)-EXAMPLE 39(4)

By the same procedure as described in example 39 using the compoundprepared in example 15(3), example 15(4), example 15(13) or example15(14) in place of the compound prepared in example 15, the followingcompounds of the present invention were given.

EXAMPLE 39(1)(Z)-2-(6-t-butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.17 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.30 (br, 1H),7.62 (d, J=8.5 Hz, 1H), 7.38 (d, J=2.0 Hz, 1H), 7.12 (dd, J=8.5, 2.0 Hz,1H), 6.61 (br, 1H), 5.56 (s, 1H), 2.80 (s, 2H), 2.26 (m, 1H), 1.89-1.78(m, 4H), 1.68 (m, 1H), 1.58-1.24 (m, 20H).

EXAMPLE 39(2)(Z)-2-(6-t-butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=3:1).

EXAMPLE 39(3)(Z)-2-(6-t-butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.48 (br, 1H),7.64 (d, J=9.0 Hz, 1H), 7.42 (d, J=2.0 Hz, 1H), 7.10 (dd, J=9.0, 2.0 Hz,1H), 6.60 (br, 1H), 5.71 (s, 1H), 2.80 (s, 2H), 2.05 (br, 3H), 1.91 (br,6H), 1.74 (br, 6H), 1.53 (s, 9H), 1.28 (s, 6H).

EXAMPLE 39(4)(Z)-2-(6-t-butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.41 (methylene chloride:methanol=10:1); NMR (CDCl₃): δ 11.84(br, 1H), 9.14 (d, J=1.5 Hz, 1H), 8.65 (dd, J=5.0, 1.5 Hz, 1H), 8.21(ddd, J=8.5, 1.5, 1.5 Hz, 1H), 7.74 (d, J=8.5 Hz, 1H), 7.49 (d, J=2.0Hz, 1H), 7.36 (dd, J=8.5, 5.0 Hz, 1H), 7.17 (dd, J=8.5, 2.0 Hz, 1H),6.67 (s, 1H), 6.21 (s, 1H), 2.88 (s, 2H), 1.54 (s, 9H), 1.37 (s, 6H).

EXAMPLE 40(Z)-2-(6-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To the compound prepared in example 39 (1.04 g) was added a 4N solutionof hydrogen chloride in dioxane (20 ml) and the mixture was stirred for2 hours at room temperature. To the reaction mixture was added methanoluntil homogeneous and the mixture was stirred for 1 hour at 50° C. Tothe reaction mixture was added a saturated aqueous solution of sodiumbicarbonate and was extracted with a mixture of ethyl acetate andtetrahydrofuran. The extract was washed with brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=3:1→chloroform) togive the compound of the present invention (458 mg) having the followingphysical data.

TLC: Rf0.29 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.84 (brs, 1H),7.96-7.91 (m, 2H), 7.64 (d, J=8.4 Hz, 1H), 7.44-7.39 (m, 3H), 6.59 (dd,J=8.4, 2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 6.21 (s, 1H), 4.00 (brs,2H), 2.78 (s, 2H), 1.35 (s, 6H).

EXAMPLE 40(1)-EXAMPLE 40(4)

By the same procedure as described in example 40 using the compoundprepared in example 39(1)-example 39(4) in place of the compoundprepared in example 39, the compounds of the present invention weregiven.

EXAMPLE 40(1)(Z)-2-(6-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.11 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.33 (br, 1H),7.52 (d, J=8.5 Hz, 1H), 6.55 (dd, J=8.5, 2.5 Hz, 1H), 6.42 (d, J=2.5 Hz,1H), 5.50 (s, 1H), 3.94 (br, 2H), 2.72 (s, 2H), 2.25 (tt, J=11.5, 3.5Hz, 1H), 1.89-1.78 (m, 4H), 1.68 (m, 1H), 1.58-1.20 (m, 1H).

EXAMPLE 40(2)(Z)-2-(6-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.14 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.51 (d, J=8.5 Hz, 1H), 6.55 (dd, J=8.5, 2.5 Hz, 1H), 6.42 (d, J=2.5 Hz,1H), 5.47 (s, 1H), 3.93 (br, 2H), 2.71 (s, 2H), 2.41 (tt, J=9.5, 4.0 Hz,1H), 1.94-1.88 (m, 2H), 1.82-1.45 (m, 10H), 1.28 (s, 6H).

EXAMPLE 40(3)(Z)-2-(6-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.12 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.54 (d, J=8.5 Hz, 1H), 6.56 (dd, J=8.5, 2.5 Hz, 1H), 6.42 (d, J=2.5 Hz,1H), 5.65 (s, 1H), 3.94 (br, 2H), 2.71 (s, 2H), 2.05 (br, 3H), 1.91 (br,6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 40(4)(Z)-2-(6-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.39 (methylene chloride:methanol=10:1); NMR (CDCl₃): δ 11.86(br, 1H), 9.13 (dd, J=2.0, 1.0 Hz, 1H), 8.64 (dd, J=4.5, 2.0 Hz, 1H),8.21 (ddd, J=8.0, 2.0, 2.0 Hz, 1H), 7.63 (d, J=8.5 Hz, 1H), 7.35 (ddd,J=8.0, 4.5, 1.0 Hz, 1H), 6.61 (dd, J=8.5, 2.5 Hz, 1H), 6.47 (d, J=2.5Hz, 1H), 6.16 (s, 1H), 4.04 (br, 2H), 2.80 (s, 2H), 1.37 (s, 6H).

EXAMPLE 41(Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 38 (49 mg) intetrahydrofuran (2 ml) were added acetic acid (0.10 ml), a 35% aqueoussolution of formaldehyde (0.14 ml) and sodium borotriacetoxyhydride (340mg) and the mixture was stirred overnight at room temperature. Thereaction mixture was added to a saturated aqueous solution of sodiumbicarbonate and the mixture was extracted with ethyl acetate. Theextract was washed with brine, dried over anhydrous magnesium sulfateand concentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=9:1) to give the compound of thepresent invention (25 mg) having the following physical data.

TLC: Rf0.54 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.90 (brs, 1H),7.97-7.90 (m, 2H), 7.46-7.41 (m, 3H), 7.13 (d, J=2.7 Hz, 1H), 7.07 (d,J=8.4 Hz, 1H), 6.84 (dd, J=8.4, 2.7 Hz, 1H), 6.28 (s, 1H), 3.01 (s, 6H),2.79 (s, 2H), 1.35 (s, 6H).

EXAMPLE 41(1)-EXAMPLE 41(2)

By the same procedure as described in example 41 using the compoundprepared in example 11(133) or example 11(134) in place of the compoundprepared in example 38, the following compounds of the present inventionwere given.

EXAMPLE 41(1)(Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.97 (br, 1H),8.00 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.5 Hz, 2H), 7.30 (s, 1H), 6.66 (s,1H), 6.14 (s, 1H), 3.96 (s, 3H), 2.85 (s, 8H), 1.38 (s, 6H).

EXAMPLE 41(2)(Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.56 (br, 1H),7.25 (s, 1H), 6.60 (s, 1H), 5.66 (s, 1H), 3.93 (s, 3H), 2.83 (s, 6H),2.76 (s, 2H), 2.06 (br, 3H), 1.92 (br, 6H), 1.75 (br, 6H), 1.30 (s, 6H).

REFERENCE EXAMPLE 94-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-one

To a solution of 3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-one (200mg) and N-bromosuccinimide (223 mg) in carbon tetrachloride (5 ml) wasadded benzoylperoxide (24 mg) and the mixture was stirred overnight atroom temperature, and refluxed for 1 hour. The reaction mixture wasallowed to cool and the precipitate was removed. The filtrate was washedwith a mixture of hexane and ethyl acetate (4/1) to give the compound ofthe present invention (196 mg) having the following physical data.

TLC: Rf0.37 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 8.10 (dd, J=7.5,1.5 Hz, 1H), 7.54 (ddd, J=7.5, 7.5, 1.5 Hz, 1H), 7.46 (ddd, J=7.5, 7.5,1.5 Hz, 1H), 7.39 (dd, J=7.5, 1.5 Hz, 1H), 5.98 (br, 1H), 5.11 (s, 1H),1.59 (s, 3H), 1.37 (s, 3H).

REFERENCE EXAMPLE 10 4-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-one

To a solution of the compound prepared in reference example 9 (6.57 g)and sodium acetate (21.2 g) in dioxane (100 ml) and water (20 ml) andthe mixture was refluxed for 3 days. To the reaction mixture was addedpotassium carbonate (10.6 g) and the mixture was stirred overnight atroom temperature. The reaction mixture was concentrated. To the residuewas added ethyl acetate and the precipitate was removed. The aqueouslayer of the filtrate was extracted with ethyl acetate. The combinedorganic layer was washed with brine, dried over anhydrous magnesiumsulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=3:2) to give thecompound of the present invention (2 g) having the following physicaldata.

TLC: Rf0.28 (ethyl acetate:hexane=1:1).

REFERENCE EXAMPLE 114-t-butyldimethylsilyloxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-one

To a solution of the compound prepared in reference example 10 (1.0 g)and t-butyldimethylsilyl chloride (784 mg) in methylene chloride (10 ml)was added imidazole (708 mg) and the mixture was stirred for 2 hours atroom temperature. To the reaction mixture were added methylene chloride(10 ml), dimehylformamide (5 ml) and triethylamine (0.5 ml) and themixture was stirred overnight. The reaction mixture was poured intowater and extracted with a mixture of hexane and ethyl acetate (1/3).The extract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=3:1) togive the compound of the present invention (632 mg) having the followingphysical data.

TLC: Rf0.61 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 8.02 (dd, J=7.5,1.5 Hz, 1H), 7.52 (ddd, J=7.5, 7.5, 1.5 Hz, 1H), 7.45-7.35 (m, 2H), 5.80(br, 1H), 4.65 (s, 1H), 1.26 (s, 3H), 1.18 (s, 3H), 0.93 (s, 9H), 0.14(s, 3H), 0.00 (s, 3H).

REFERENCE EXAMPLE 12(Z)-2-(4-t-butyldimethylsilyloxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

By the same procedure as described in reference example 6→example 11using the compound prepared in reference example 11 in place of thecompound prepared in reference example 5, the compound of the presentinvention was given.

TLC: Rf0.56 (chloroform:hexane=1:5); NMR (CDCl₃): δ 11.66 (br, 1H), 7.95(m, 2H), 7.79 (d, J=8.0 Hz, 1H), 7.55-7.30 (m, 6H), 6.32 (s, 1H), 4.65(s, 1H), 1.36 (s, 3H), 1.15 (s, 3H), 0.95 (s, 9H), 0.15 (s, 3H), 0.06(s, 3H).

EXAMPLE 42(Z)-2-(3,3-dimethyl-4-hydroxy-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in reference example 12 (810 mg)in tetrahydrofuran (10 ml) was added tetrabutylammonium fluoride (4.0ml, 1.0 M in tetrahydrofuran) at 0° C. and the mixture was stirred for 3hours at room temperature. The reaction mixture was poured intoice-water and the mixture was extracted with ethyl acetate. The extractwas washed with hydrochloric acid, a saturated aqueous solution ofsodium bicarbonate, water and brine successively, dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=4:1→3:2) to give thecompound of the present invention (566 mg) having the following physicaldata.

TLC: Rf0.52 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.65 (br, 1H),7.94 (m, 2H), 7.85 (d, J=8.0 Hz, 1H), 7.60-7.40 (m, 6H), 6.37 (s, 1H),4.55 (d, J=7.5 Hz, 1H), 2.11 (d, J=7.5 Hz, 1H), 1.37 (s, 3H), 1.33 (s,3H).

EXAMPLE 43(Z)-2-(3,3-dimethyl-4-oxo-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-one

To a solution of the compound prepared in example 42 (428 mg) inmethylene chloride (40 ml) was added pyridinium chlorochromate (2793 mg)at room temperature and the mixture was stirred for 6 hours at roomtemperature. The reaction mixture was filtered. The filtrate wasconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=9:1→5:1) to give the compound of thepresent invention (137 mg) having the following physical data.

TLC: Rf0.31 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 12.22 (br, 1H),8.17 (dd, J=7.5, 1.5 Hz, 1H), 8.06 (m, 1H), 7.97 (m, 2H), 7.76 (ddd,J=7.5, 7.5, 1.5 Hz, 1H), 7.68 (ddd, J=7.5, 7.5, 1.5 Hz, 1H), 7.55-7.40(m, 3H), 6.60 (s, 1H), 1.60 (s, 6H).

EXAMPLE 44 EXAMPLE 44(4)

By converting the compounds prepared in example 11(80) or example 14(8)to corresponding salts by a conventional method, the following compoundsof the present invention were given.

EXAMPLE 44(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)ethan-1-one,hydrochloride

TLC: Rf0.25 (ethyl acetate:hexane=1:10); NMR (CDCl₃): δ 7.50 (d, J=8.0Hz, 1H), 7.35 (dd, J=8.0, 2.0 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 4.6 (br,2H), 2.95 (s, 2H), 2.09 (m, 3H), 1.95 (m, 6H), 1.75 (m, 6H), 1.49 (s,6H).

EXAMPLE 44(1)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)ethan1-one, methanesulfonate

TLC: Rf0.25 (ethyl acetate:hexane=1:10); NMR (CDCl₃): δ 7.47 (d, J=8.5Hz, 1H), 7.39 (dd, J=8.5, 2.0 Hz, 1H), 7.33 (s, 1H), 4.6 (br, 2H), 3.02(s, 2H), 2.85 (s, 3H), 2.12 (m, 3H), 1.96 (m, 6H), 1.76 (m, 6H), 1.55(s, 6H).

EXAMPLE 44(2)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)ethan-1-one,bishydrochloride

TLC: Rf0.68 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 7.22 (s, 1H),6.80 (s, 1H), 2.91 (s, 2H), 2.12 (m, 3H), 1.98 (m, 6H), 1.76 (m, 6H),1.59 (s, 6H).

EXAMPLE 44(3)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)ethan-1-one,bismethanesulfonate

TLC: Rf0.68 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 7.58 (s, 1H),7.30 (s, 1H), 4.94 (br, 6H), 2.99 (s, 2H), 2.85 (s, 6H), 2.09 (m, 3H),1.95 (m, 6H), 1.74 (m, 6H), 1.53 (s, 6H).

EXAMPLE 44(4)(Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-1-(adamantan-1-yl)ethan-1-onemethanesulfonate

TLC: Rf0.68 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 7.34 (s, 1H),7.15 (s, 1H), 4.81 (br, 2H), 3.46 (br, 3H), 2.86 (s, 2H), 2.83 (s, 3H),2.05 (m, 3H), 1.96 (m, 6H), 1.73 (m, 6H), 1.46 (s, 6H).

EXAMPLE 45(Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

To a solution of the compound prepared in example 30(9) (488 mg) in1,4-dioxane (10 ml) was added pyridine (0.36 ml) at room temperature andto the mixture was added trifluoroacetic anhydride (0.32 ml) undercooling with ice and the mixture was stirred for 15 minutes. To thereaction mixture was added water and the mixture was extracted withethyl acetate. The extract was washed with water and brine successively,dried over anhydrous magnesium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (hexane:ethylacetate=15:1→13:1) to give the compound of the present invention (305mg) having the following physical data.

TLC: Rf0.44 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.18 (br, 1H),7.80 (d, J=8.5 Hz, 1H), 7.58 (dd, J=8.5, 1.5 Hz, 1H), 7.48 (d, J=1.5 Hz,1H), 5.64 (s, 1H), 2.87 (s, 2H), 2.31 (tt, J=11.5, 3.5 Hz, 1H),1.89-1.80 (m, 4H), 1.70 (m, 1H), 1.51-1.20 (m, 11H).

EXAMPLE 45(1)-EXAMPLE 45(2)

By the same procedure as described in example 45 using the compoundprepared in example 30(10) or example 30(11) in place of the compoundprepared in example 30(9), the following compounds of the presentinvention were given.

EXAMPLE 45(1)(Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.09 (br, 1H),7.79 (d, J=8.0 Hz, 1H), 7.58 (dd, J=8.0, 1.5 Hz, 1H), 7.47 (d, J=1.5 Hz,1H), 5.61 (s, 1H), 2.87 (s, 2H), 2.48 (tt, J=10.0, 4.0 Hz, 1H),1.94-1.87 (m, 2H), 1.83-1.45 (m, 10H), 1.29 (s, 6H).

EXAMPLE 45(2)(Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.81 (d, J=8.0 Hz, 1H), 7.59 (dd, J=8.0, 1.5 Hz, 1H), 7.48 (d, J=1.5 Hz,1H), 5.80 (s, 1H), 2.87 (s, 2H), 2.06 (br, 3H), 1.90 (br, 6H), 1.74 (br,6H), 1.30 (s, 6H).

EXAMPLE 46 EXAMPLE 46(5)

By the same procedure as described in example II using a derivativecorresponding to the compound prepared in reference example 6 and aderivative corresponding to benzoylmethyl bromide, the compounds of thepresent invention were given.

EXAMPLE 46(Z)-2-(7-t-butylsulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.46 (brs, 1H),8.20 (d, J=1.8 Hz, 1H), 7.88 (dd, J=8.1, 1.8 Hz, 1H), 7.30 (d, J=8.1 Hz,1H), 5.79 (s, 1H), 4.53 (brs, 1H), 2.89 (s, 2H), 2.09-2.03 (m, 3H),1.92-1.88 (m, 6H), 1.77-1.72 (m, 6H), 1.29 (s, 6H), 1.27 (s, 9H).

EXAMPLE 46(1)(Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.26 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.25 (brs, 1H),7.85 (s, 1H), 6.68 (s, 1H), 5.51 (s, 1H), 4.05 (ddd, J=11.4, 4.2, 2.4Hz, 2H), 3.95 (s, 3H), 3.46 (dt, J=3.0, 11.4 Hz, 2H), 2.80 (s, 2H), 2.52(tt, J=11.1, 4.5 Hz, 1H), 1.92-1.72 (m, 4H), 1.31 (s, 6H).

EXAMPLE 46(2)(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-(6-chloropyridin-3-yl)ethan-1-one

TLC: Rf0.20 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.86 (br, 1H),8.92 (dd, J=2.5, 0.5 Hz, 1H), 8.17 (dd, J=8.5, 2.5 Hz, 1H), 7.75 (s,1H), 7.38 (dd, J=8.5, 0.5 Hz, 1H), 6.71 (s, 1H), 6.16 (s, 1H), 4.74 (d,J=6.5 Hz, 2H), 3.94 (s, 3H), 2.90 (s, 2H), 2.20 (t, J=6.5 Hz, 1H), 1.38(s, 6H).

EXAMPLE 46(3)(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.37 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.09 (br, 1H),8.08 (s, 1H), 7.64 (s, 1H), 5.63 (s, 1H), 4.06 (m, 2H), 3.47 (m, 2H),2.95 (s, 2H), 2.59 (m, 1H), 1.90-1.70 (m, 4H), 1.32 (s, 6H).

EXAMPLE 46(4)(Z)-2-(7-t-butylsulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=1:1); NMR (CDCl₃) δ 11.25 (brs, 1H),8.21 (d, J=2.0 Hz, 1H), 7.90 (dd, J=8.0, 2.0 Hz, 1H), 7.32 (d, J=8.0 Hz,1H), 5.67 (s, 1H), 4.57 (s, 1H), 4.05 (m, 2H), 3.48 (dt, J=11.5, 3.0 Hz,2H), 2.91 (s, 2H), 2.57 (m, 1H), 1.90-1.70 (m, 4H), 1.31 (s, 6H), 1.26(s, 9H).

EXAMPLE 46(5)(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.88 (brs, 1H),8.02 (d, J=8.7 Hz, 2H), 7.91 (d, J=2.1 Hz, 1H), 7.74 (d, J=8.7 Hz, 2H),7.58 (dd, J=8.1, 2.1 Hz, 1H), 7.13 (d, J=8.1 Hz, 1H), 6.20 (s, 1H), 2.87(s, 2H), 1.37 (s, 6H).

EXAMPLE 47-EXAMPLE 47(6)

By the same procedure as described in example 5 using the compoundprepared in example 12(7), 12(9), 11(117), 11(201)-11(203) in place ofthe compound prepared in example 1(18), the compounds of the presentinvention were given.

EXAMPLE 47(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.28 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.17 (br, 1H),7.18 (d, J=2.4 Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 6.88 (dd, J=2.4, 7.8 Hz,1H), 5.53 (s, 1H), 2.75 (s, 2H), 2.44 (m, 1H), 1.92-1.42 (m, 12H), 1.27(s, 6H).

EXAMPLE 47(1)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.16 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.61 (d, J=8.4 Hz, 1H), 6.76 (dd, J=2.4, 8.4 Hz, 1H), 6.66 (d, J=2.4 Hz,1H), 5.55 (s, 1H), 2.77 (s, 2H), 2.26 (m, 1H), 1.92-1.22 (m, 16H).

EXAMPLE 47(2)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.18 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.25 (br, 1H),7.60 (d, J=8.7 Hz, 1H), 6.75 (dd, J=2.4, 8.7 Hz, 1H), 6.64 (d, J=2.4 Hz,1H), 5.51 (s, 1H), 2.77 (s, 2H), 2.43 (m, 1H), 1.96-1.40 (m, 12H), 1.28(s, 6H).

EXAMPLE 47(3)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.09 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.50 (br, 1H),7.63 (d, J=8.4 Hz, 1H), 6.76 (dd, J=2.4, 8.4 Hz, 1H), 6.64 (d, J=2.4 Hz,1H), 5.69 (s, 1H), 5.53 (br, 1H), 2.77 (s, 2H), 2.05 (br, 3H), 1.91-1.90(m, 6H), 1.74 (br, 6H), 1.28 (s, 6H).

EXAMPLE 47(4)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.42 (br, 1H),7.14 (s, 1H), 6.91 (s, 1H), 5.67 (s, 1H), 4.98 (s, 1H), 2.71 (s, 2H),2.28 (s, 3H), 2.04 (br, 3H), 1.90 (br, 6H), 1.73 (br, 6H), 1.26 (s, 6H).

EXAMPLE 47(5)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.16 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.24 (br, 1H),7.11 (s, 1H), 6.90 (s, 1H), 5.53 (s, 1H), 5.19-5.15 (br, 1H), 2.71 (s,2H), 2.32-2.20 (m, 4H), 1.92-1.20 (m, 16H).

EXAMPLE 47(6)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=5:1); NMR (CDCl₃): δ 11.16 (br, 1H),7.11 (s, 1H), 6.91 (s, 1H), 5.49 (s, 1H), 4.86 (br, 1H), 2.71 (s, 2H),2.43 (m, 1H), 2.27 (s, 3H), 1.96-1.42 (m, 12H), 1.26 (s, 6H).

EXAMPLE 48(Z)-2-(7-(1-hydroxy-1-methylethyl)-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

By the same procedure as described in example 22 using the compoundprepared in example 11(181) in place of the compound prepared in example11(7), the compound of the present invention having the followingphysical data was given.

TLC: Rf0.21 (ethyl acetate:hexane=1:5); NMR (CDCl₃): δ 11.28 (br, 1H),7.68 (s, 1H), 6.68 (s, 1H), 5.52 (s, 1H), 3.95 (s, 3H), 3.65 (s, 1H),2.79 (s, 2H), 2.46 (m, 1H), 2.00-1.40 (m, 12H), 1.65 (s, 6H), 1.29 (s,6H).

EXAMPLE 49(Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

By the same procedure as described in example 13 using the compoundprepared in example 46(1) in place of the compound prepared in example12, the compound of the present invention having the following physicaldata was given.

TLC: Rf0.49 (hexane:ethyl acetate=1:4).

EXAMPLE 50(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

By the same procedure as described in example 28 using the compoundprepared in example 49 in place of the compound prepared in example 13,the compound of the present invention having the following physical datawas given.

TLC: Rf0.34 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.30 (brs, 1H),7.64 (s, 1H), 6.66 (s, 1H), 5.59 (s, 1H), 4.71 (d, J=6.0 Hz, 2H), 4.05(m, 2H), 3.92 (s, 3H), 3.46 (dt, J=3.0, 11.4 Hz, 2H), 2.83 (s, 2H), 2.51(tt, J=10.8, 4.5 Hz, 1H), 2.16 (t, J=6.0 Hz, 1H), 1.92-1.72 (m, 4H),1.31 (s, 6H).

EXAMPLE 51(Z)-2-(7-(1-hydroxyethyl)-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one

To a solution of the compound prepared in example 13(11) (140 mg) intetrahydrofuran (5 ml) was added methyl lithium (1.7 μL, 1.04 M inether) at −78° C. and the mixture was stirred for 10 minutes at −78° C.To the reaction mixture was added a saturated aqueous solution ofammonium chloride and the mixture was extracted with ethyl acetate. Theextract was washed with water and brine successively, dried overanhydrous magnesium sulfate and concentrated. The residue was washedwith a mixture of hexane and ethyl acetate (20/1) to give the compoundof the present invention (95 mg) having the following physical data.

TLC: Rf0.25 (ethyl acetate:hexane=1:2); NMR (CDCl₃): δ 11.24 (br, 1H),7.71 (s, 1H), 6.63 (s, 1H), 5.56 (s, 1H), 5.13 (m, 1H), 3.90 (s, 3H),2.80 (s, 2H), 2.46 (m, 1H), 2.36 (d, J=5.0 Hz, 1H), 2.00-1.40 (m, 12H),1.53 (d, J=3.5 Hz, 3H), 1.29 (s, 3H), 1.28 (s, 3H).

EXAMPLE 52(Z)-2-(7-bromomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

To a solution of the compound prepared in example 28(6) (400 mg) inmethylene chloride (10 ml) were added triphenylphosphine (349 mg) andcarbon tetrabromide (550 mg) and the mixture was stirred for 1 hour atroom temperature. To the reaction mixture were added triphenylphosphine(350 mg) and carbon tetrabromide (546 mg) and the mixture was stirredfor 10 minutes at room temperature. To the reaction mixture were added asaturated aqueous solution of sodium bicarbonate and t-butyl methylether and the mixture was washed with water and brine successively,dried over anhydrous magnesium sulfate and then to the mixture was addeda 4N solution of hydrogen chloride in ethyl acetate (1 ml) and themixture was concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=9:1) to give thecompound of the present invention (220 mg) having the following physicaldata.

TLC: Rf0.61 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.49 (brs, 1H),7.70 (d, J=1.5 Hz, 1H), 7.42 (dd, J=7.8, 1.5 Hz, 1H), 7.18 (d, J=7.8 Hz,1H), 5.78 (s, 1H), 4.64 (s, 2H), 2.83 (s, 2H), 2.10-2.03 (m, 3H),1.94-1.90 (m, 6H), 1.78-1.73 (m, 6H), 1.29 (s, 6H).

EXAMPLE 53(Z)-2-(7-methoxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)1-(adamantan-1-yl)ethan-1-one

To a suspension of sodium hydride (54 mg) in dimethylformamide (3 ml)was added methanol (0.25 ml) under cooling with ice and the mixture wasstirred for 30 minutes at room temperature. The reaction mixture wasagain cooled with ice and to the mixture was added a solution of thecompound prepared in example 52 (220 mg) in tetrahydrofuran (3 ml) andthe mixture was stirred for 3 hours at room temperature. To the reactionmixture was added ice and the mixture was extracted with a mixture ofhexane and ethyl acetate. The extract was washed with water and brine,dried over anhydrous magnesium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (hexane:ethylacetate=9:1) to give the compound of the present invention (56 mg)having the following physical data.

TLC: Rf0.42 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.52 (brs, 1H),7.66 (brs, 1H), 7.37 (dd, J=7.8, 1.8 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H),5.79 (s, 1H), 4.49 (s, 2H), 3.44 (s, 3H), 2.83 (s, 2H), 2.09-2.03 (m,3H), 1.94-1.90 (m, 6H), 1.77-1.73 (m, 6H), 1.28 (s, 6H).

EXAMPLE 54(Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

To a suspension of the compound prepared in example 46(2) (55 mg) andsodium acetate (17 mg) in methanol (5.5 ml) was added 1% palladiumcarbon under atmosphere of argon at room temperature, and underatmosphere of hydrogen the mixture was stirred for 6 hours. The reactionmixture was filtered over celite. The filtrate was concentrated. To theresidue was added ethyl acetate and the mixture was washed with asaturated aqueous solution of sodium bicarbonate, water and brinesuccessively and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=1:1→ethyl acetate) togive the compound of the present invention (35 mg) having the followingphysical data.

TLC: Rf0.06 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.85 (br, 1H),9.15 (dd, J=2.0, 1.0 Hz, 1H), 8.65 (dd, J=4.5, 2.0 Hz, 1H), 8.21 (ddd,J=7,5, 2.0, 2.0 Hz, 1H), 7.77 (s, 1H), 7.36 (ddd, J=7.5, 4.5, 1.0 Hz,1H), 6.70 (s, 1H), 6.23 (s, 1H), 4.74 (s, 2H), 3.94 (s, 3H), 2.90 (s,2H), 2.32 (br, 1H), 1.38 (s, 6H).

EXAMPLE 55(Z)-2-(7-sulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one

To a solution of the compound prepared in example 46 (369 mg) inmethanol (12 ml) was added concentrated hydrochloric acid (6 ml) and themixture was refluxed for 8 hours at 100° C. The mixture was allowed tocool to room temperature and the reaction mixture was cooled with iceand it was neutralized with a 5N aqueous solution of sodium hydroxide,and was extracted with a mixture of ethyl acetate, tetrahydrofuran andmethanol. The extract was washed with brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was washed with t-butylmethyl ether to give the compound of the present invention (295 mg)having the following physical data.

TLC: Rf0.32 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 11.45 (brs,1H), 8.18 (d, J=1.8 Hz, 1H), 7.86 (dd, J=7.8, 1.8 Hz, 1H), 7.49 (s, 2H),7.48 (d, J=7.8 Hz, 1H), 5.80 (s, 1H), 2.94 (s, 2H), 2.04-1.97 (m, 3H),1.83-1.78 (m, 6H), 1.75-1.63 (m, 6H), 1.22 (s, 6H).

EXAMPLE 55(1)(Z)-2-(7-sulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(tetrahydropyran-4-yl)ethan-1-one

By the same procedure as described in example 55 using the compoundprepared in example 46(4) in place of the compound prepared in example46, the compound of the present invention having the following physicaldata was given.

TLC: Rf0.14 (ethyl acetate:hexane=1:1); NMR (CDCl₃): δ 11.23 (br, 1H),8.25 (d, J=2.0 Hz, 1H), 7.94 (dd, J=8.0, 2.0 Hz, 1H), 7.36 (d, J=8.0 Hz,1H), 5.68 (s, 1H), 4.91 (br, 2H), 4.05 (m, 2H), 3.47 (m, 2H), 2.95 (s,2H), 2.59 (m, 1H), 1.90-1.70 (m, 4H), 1.32 (s, 6H).

REFERENCE EXAMPLE 13 2-bromo-5-methoxybenzoic acid, methyl ester

To a solution of 2-bromo-5-methoxybenzoic acid (15.0 g) indimethylformamide (100 ml) were added potassium bicarbonate (7.83 g) andmethyl iodide (8.12 ml) and the mixture was stirred for 20 hours at roomtemperature. The reaction mixture was diluted with water and wasextracted with a mixture of ethyl acetate and hexane (1/1). The extractwas washed with water, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=8:1) to give the title compound (16.3g) having the following physical data.

TLC: Rf0.80 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.53 (d, J=9.0Hz, 1H), 7.31 (d, J=3.0 Hz, 1H), 6.89 (dd, J=9.0, 3.0 Hz, 1H), 3.93 (s,3H), 3.82 (s, 3H).

REFERENCE EXAMPLE 14 2-cyano-5-methoxybenzoic acid, methyl ester

In 1-methylpyrrolidin-2-one (60 ml) was dissolved the compound preparedin reference example 13 (5.07 g) and thereto was added copper cyanide(2.79 g) and the mixture was stirred for 3 hours at 150° C. The mixturewas cooled to room temperature and thereto was added water and t-butylethyl ether. The precipitate was collected, and it was suspended inwater (200 ml) and to the mixture was added sodium cyanide (10.9 g) andthe mixture was stirred for 2 hours at room temperature. The reactionmixture was filtered over celite. The filtrate was extracted with ethylacetate. The extract was washed with water, dried over anhydrousmagnesium sulfate and concentrated to give the title compound (2.71 g)having the following physical data.

TLC: Rf0.49 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.72 (d, J=8.4Hz, 1H), 7.62 (d, J=2.7 Hz, 1H), 7.13 (dd, J=8.4, 2.7 Hz, 1H), 4.00 (s,3H), 3.92 (s, 3H).

REFERENCE EXAMPLE 15 2-cyano-5-methoxybenzoic acid

To a solution of the compound prepared in reference example 14 (2.48 g)in methanol (10 ml) and a 2N aqueous solution of sodium hydroxide (9.75ml) and the mixture was stirred for 2 hours at room temperature. Thereaction mixture was neutralized with 2N hydrochloric acid (9.75 ml) andthe mixture was concentrated. The residue was washed with water andether to give the title compound (1.50 g) having the following physicaldata.

TLC: Rf0.24 (chloroform:methanol=10:1); NMR (DMSO-d₆): δ 7.89 (d, J=8.4Hz, 1H), 7.53 (d, J=2.7 Hz, 1H), 7.32 (dd, J=8.4, 2.7 Hz, 1H), 3.89 (s,3H), 3.31 (brs, 1H).

REFERENCE EXAMPLE 16 6-methoxy-3,3-dimethylisoindolin-1-one

Under atmosphere of argon, to a solution of the compound prepared inreference example 15 (1.00 g) in tetrahydrofuran (20 ml) was addedmethyl magnesium chloride (28.3 ml; 3.0 M in tetrahydrofuran) at −78° C.dropwise and the mixture was stirred for 12 hours at room temperature.The reaction mixture was poured into a 1N hydrochloric acid at 0° C. andthe mixture was extracted with ethyl acetate. The extract was washedwith water, dried over anhydrous magnesium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=2:1→1:1→ethyl acetate) to give the title compound(146 mg) having the following physical data.

TLC: Rf0.62 (ethyl acetate); NMR (CDCl₃): δ 7.29 (d, J=2.4 Hz, 1H), 7.28(d, J=8.4 Hz, 1H), 7.12 (dd, J=8.4, 2.4 Hz, 1H), 6.60 (br, s, 1H), 3.86(s, 3H), 1.54 (s, 6H).

REFERENCE EXAMPLE 17 6-methoxy-3,3-dimethylisoindolin-1-thione

To a solution of the compound prepared in reference example 16 (146 mg)in toluene (3.0 ml) was added Lawesson reagent(2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphethan-2,4-disulfide)(155 mg) and the mixture was refluxed for 1 hour. The reaction mixturewas cooled to room temperature and purified by column chromatography onsilica gel (hexane:ethyl acetate=5:1→3:1) to give the title compound(106 mg) having the following physical data.

TLC: Rf0.67 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.17 (br, s, 1H),7.49 (d, J=2.4 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.15 (dd, J=8.4, 2.4 Hz,1H), 3.90 (s, 3H), 1.56 (s, 6H).

EXAMPLE 56(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

To m-xylene were added the compound prepared in reference example 17(246 mg) and 4-nitrophenacyl bromide (307 mg) and the mixture wasstirred for 15 hours at room temperature. To the reaction mixture wereadded triethylamine (0.22 ml), triphenylphosphine (330 mg) andtriethylamine (0.22 ml) successively and the mixture was refluxed for 1hour. The reaction mixture was allowed to cool to room temperature andit was purified by column chromatography on silica gel (hexane:ethylacetate=4:1→2:1→1:1) to give the compound of the present inventionhaving the following physical data.

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.60 (br, s,1H), 8.30 (d, J=9.0 Hz, 2H), 8.12 (d, J=9.0 Hz, 2H), 7.33 (d, J=8.4 Hz,1H), 7.22 (d, J=2.1 Hz, 1H), 7.13 (dd, J=8.4, 2.1 Hz, 1H), 6.30 (s, 1H),3.91 (s, 3H), 1.60 (s, 6H).

EXAMPLE 56(1)-EXAMPLE 56(4)

By the same procedure as described in example 56 using a correspondingderivative in place of 4-nitrophenacyl bromide, the following compoundsof the present invention were given.

EXAMPLE 56(1)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.56 (br, s,1H), 8.07 (d, J=8.4 Hz, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz,1H), 7.21 (d, J=2.4 Hz, 1H), 7.12 (dd, J=8.4, 2.4 Hz, 1H), 6.28 (s, 1H),3.91 (s, 3H), 1.59 (s, 6H).

EXAMPLE 56(2)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.33 (br, s,1H), 7.99 (d, J=8.7 Hz, 2H), 7.29 (d, J=8.1 Hz, 1H), 7.21 (d, J=2.1 Hz,1H), 7.08 (dd, J=8.1, 2.1 Hz, 1H), 6.96 (d, J=8.7 Hz, 2H), 6.29 (s, 1H),3.90 (s, 3H), 3.87 (s, 3H), 1.56 (s, 6H).

EXAMPLE 56(3)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.29 (br, s,1H), 7.70 (dd, J=7.8, 2.1 Hz, 1H), 7.37 (m, 1H), 7.29 (d, J=8.1 Hz, 1H),7.14 (d, J=2.4 Hz, 1H), 7.06 (dd, J=8.1, 2.4 Hz, 1H), 7.05-6.95 (m, 2H),6.25 (s, 1H), 3.92 (s, 3H), 3.86 (s, 3H), 1.57 (s, 6H).

EXAMPLE 56(4)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.68 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 9.96 (br, s, 1H),7.25 (d, J=8.4 Hz, 1H), 7.10 (d, J=2.4 Hz, 1H), 7.04 (dd, J=8.4, 2.4 Hz,1H), 5.63 (s, 1H), 3.87 (s, 3H), 2.34 (m, 1H), 1.95-1.80 (m, 4H), 1.69(m, 1H), 1.51 (s, 6H), 1.55-1.20 (m, 5H).

REFERENCE EXAMPLE 18 2-cyano-4-methoxyphenol

To a solution of 2-hydroxy-5-methoxybenzaldehyde (4.00 g) in formic acid(30 ml) were added hydroxylamine hydrochloride (2.01 g) and sodiumformate (3.22 g) at room temperature and the mixture was refluxed for 2hours. The reaction mixture was concentrated. the residue was dilutedwith water and was extracted with t-butyl methyl ether. The extract waswashed with water, dried over anhydrous magnesium sulfate andconcentrated. The residue was washed with a mixture of t-butyl methylether and hexane to give the title compound (2.02 g) having thefollowing physical data.

TLC: Rf0.53 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.06 (dd, J=9.0,3.0 Hz, 1H), 6.94 (d, J=3.0 Hz, 1H), 6.91 (d, J=9.0 Hz, 1H), 5.60 (br,s, 1H), 3.78 (s, 3H).

REFERENCE EXAMPLE 19 2-cyano-4-methoxyphenyl trifluoromethanesulfonate

To a solution of the compound prepared in reference example 18 (1.00 g)in a mixture of acetonitrile (10 ml) and triethylamine (1.87 ml) wasadded N-phenylbistrifluoromethane sulfonimide (2.40 g) at 0° C. and themixture was stirred for 2.5 hours at 0° C. The reaction mixture wasdiluted with water and the mixture was extracted with ethyl acetate. Theextract was washed with water, dried over anhydrous magnesium sulfateand concentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=10:1→6:1→4:1) to give the titlecompound (2.36 g) having the following physical data.

TLC: Rf0.54 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.38 (dd, J=8.4,1.5 Hz, 1H), 7.20 (d, J=1.5 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 3.87 (s,3H).

REFERENCE EXAMPLE 20 2-cyano-4-methoxybenzoic acid

To a solution of the compound prepared in reference example 19 (2.36 g)in dimethylformamide (15 ml) were added palladium acetate (75.3 mg),1,1′-bis(diphenylphosphino)ferrocene (372 mg, DPPF) and potassiumacetate (3.29 g) and under atmosphere of carbon monooxide the mixturewas stirred for 5 hours at 60° C. The reaction mixture was diluted witha dilute hydrochloric acid. The mixture was extracted with ethylacetate. The extract was washed with brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was dissolved intoluene, and it was subjected to back extraction. The aqueous layer wasneutralized with 1N hydrochloric acid. The precipitate was washed withwater to give the title compound (600 mg) having the following physicaldata.

TLC: Rf0.37 (chloroform:methanol=10:1); NMR (DMSO-d₆): δ 8.03 (d, J=9.0Hz, 1H), 7.52 (d, J=3.0 Hz, 1H), 7.33 (dd, J=9.0, 3.0 Hz, 1H), 3.88 (s,3H), 3.31 (br, s, 1H).

EXAMPLE 57-EXAMPLE 57(4)

By the same procedure as described in reference example 16→referenceexample 17→example 56 using the compound prepared in reference example20 in place of the compound prepared in reference example 15, and acorresponding derivative in place of 4-nitrophenacyl bromide, thefollowing compounds of the present invention were given.

EXAMPLE 57(Z)-2-(5-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-phenylethan-1-one

TLC: Rf0.42 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.40 (br, s,1H), 8.01-7.96 (m, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.50-7.40 (m, 3H), 6.96(dd, J=8.4, 2.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H), 6.29 (s, 1H), 3.90 (s,3H), 1.58 (s, 6H).

EXAMPLE 57(1)(Z)-2-(5-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.51 (br, s,1H), 8.05 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz,1H), 6.98 (dd, J=8.4, 2.4 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.24 (s, 1H),3.91 (s, 3H), 1.60 (s, 6H).

EXAMPLE 57(2)(Z)-2-(5-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.27 (br, s,1H), 7.71 (dd, J=7.5, 1.8 Hz, 1H), 7.59 (d, J=8.7 Hz, 1H), 7.36 (m, 1H),7.10-6.90 (m, 3H), 6.86 (d, J=2.1 Hz, 1H), 6.22 (s, 1H), 3.92 (s, 3H),3.89 (s, 3H), 1.58 (s, 6H).

EXAMPLE 57(3)(Z)-2-(5-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-cyclohexylethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 9.96 (br, s, 1H),7.55 (d, J=8.4 Hz, 1H), 6.91 (dd, J=8.4, 2.1 Hz, 1H), 6.83 (d, J=2.1 Hz,1H), 5.59 (s, 1H), 3.88 (s, 3H), 2.31 (m, 1H), 1.95-1.85 (m, 2H),1.85-1.75 (m, 2H), 1.70 (m, 1H), 1.56 (s, 6H), 1.55-1.35 (m, 2H),1.45-1.20 (m, 3H).

EXAMPLE 57(4)(Z)-2-(5-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.31 (br, s,1H), 7.98 (d, J=9.0 Hz, 2H), 7.67 (d, J=8.7 Hz, 1H), 7.00-6.85 (m, 4H),6.26 (s, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 1.57 (s, 6H).

EXAMPLE 58(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-aminophenyl)ethan-1-one

A solution of the compound prepared in example 56 (350 mg) in aceticacid (5.5 ml) and water (0.5 ml) was stirred and to the mixture wasadded steel (465 mg) and the mixture was stirred for 2 hours at 70° C.The reaction mixture was filtered. The filtrate was diluted with ethylacetate, washed with a saturated aqueous solution of sodium bicarbonate,water and brine successively, dried over anhydrous sodium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=1:1→ethyl acetate) to give the compoundof the present invention (217 mg) having the following physical data.

TLC: Rf0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.26 (br, s,1H), 7.88 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.4 Hz, 1H), 7.20 (d, J=2.4 Hz,1H), 7.06 (dd, J=8.4, 2.4 Hz, 1H), 6.71 (d, J=8.4 Hz, 2H), 6.27 (s, 1H),3.94 (br, s, 2H), 3.90 (s, 3H), 1.55 (s, 6H).

EXAMPLE 59(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-acetylaminophenyl)ethan-1-one

A solution of the compound prepared in example 58 (68.0 mg) in pyridine(0.5 ml) and acetic anhydride (0.5 ml) was stirred for 3 hours at roomtemperature. The reaction mixture was diluted with water. Theprecipitate was collected and was washed with isopropyl ether to givethe compound of the present invention (52.7 mg) having the followingphysical data.

TLC: Rf0.16 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.39 (br, s,1H), 7.99 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.7 Hz, 2H), 7.30 (d, J=8.1 Hz,1H), 7.35-7.25 (br, 1H), 7.21 (d, J=2.4 Hz, 1H), 7.09 (dd, J=8.1, 2.4Hz, 1H), 6.30 (s, 1H), 3.91 (s, 3H), 2.21 (s, 3H), 1.56 (s, 6H).

EXAMPLE 59(1)-EXAMPLE 59(2)

By the same procedure as described in example 59 using an acid anhydridecorresponding to acetic anhydride, the following compounds of thepresent invention were given.

EXAMPLE 59(1)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-butanoylaminophenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.39 (br, s,1H), 7.99 (d, J=8.7 Hz, 2H), 7.62 (d, J=8.7 Hz, 2H), 7.30 (d, J=8.4 Hz,1H), 7.35-7.20 (br, 1H), 7.22 (d, J=2.1 Hz, 1H), 7.08 (dd, J=8.4, 2.1Hz, 1H), 6.30 (s, 1H), 3.91 (s, 3H), 2.37 (t, J=7.5 Hz, 2H), 1.79(sextet, J=7.5 Hz, 2H), 1.56 (s, 6H), 1.03 (t, J=7.5 Hz, 3H).

EXAMPLE 59(2)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-hexanoylaminophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.39 (br, s,1H), 7.99 (d, J=8.7 Hz, 2H), 7.61 (d, J=8.7 Hz, 2H), 7.30 (d, J=8.4 Hz,1H), 7.24 (br, s, 1H), 7.22 (d, J=2.1 Hz, 1H), 7.08 (dd, J=8.4, 2.1 Hz,1H), 6.30 (s, 1H), 3.91 (s, 3H), 2.39 (t, J=7.5 Hz, 2H), 1.75 (m, 2H),1.56 (s, 6H), 1.45-1.30 (m, 4H), 0.92 (t, J=6.9 Hz, 3H).

EXAMPLE 60 EXAMPLE 60(29)

By the same procedure as described in example II using a correspondingderivative in place of the compound prepared in reference example 6 anda corresponding derivative in place of benzoylmethyl bromide, thefollowing compounds of the present invention were given.

EXAMPLE 60(Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.57 (br, 1H),7.85 (d, J=2.1 Hz, 1H), 7.66 (dd, J=7.5, 1.8 Hz, 1H), 7.51 (dd, J=8.0,2.1 Hz, 1H), 7.37 (ddd, J=8.2, 7.5, 1.8 Hz, 1H), 7.08 (d, J=8.0 Hz, 1H),7.01 (m, 1H), 6.97 (d, J=8.2 Hz, 1H), 6.21 (s, 1H), 3.92 (s, 3H), 2.84(s, 2H), 1.35 (s, 6H).

EXAMPLE 60(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-fluorophenyl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.78 (br, 1H),7.94 (m, 2H), 7.32 (d, J=2.6 Hz, 1H), 7.13 (m, 2H), 7.09 (d, J=8.4 Hz,1H), 6.99 (dd, J=8.4, 2.6 Hz, 1H), 6.21 (s, 1H), 3.88 (s, 3H), 2.83 (s,2H), 1.35 (s, 6H).

EXAMPLE 60(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-chlorophenyl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.82 (br, 1H),7.88 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 7.32 (d, J=2.5 Hz, 1H),7.14 (d, J=8.5 Hz, 1H), 6.99 (dd, J=8.5, 2.5 Hz, 1H), 6.21 (s, 1H), 3.88(s, 3), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 60(3)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylphenyl)ethan-1-one

TLC: Rf0.54 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.78 (br, 1H),7.85 (d, J=7.8 Hz, 2H), 7.34 (d, J=2.5 Hz, 1H), 7.24 (d, J=7.8 Hz, 2H),7.13 (d, J=8.1 Hz, 1H), 6.98 (dd, J=8.1, 2.5 Hz, 1H), 6.27 (s, 1H), 3.88(s, 3H), 2.83 (s, 2H), 2.40 (s, 3H), 1.35 (s, 6H).

EXAMPLE 60(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.73 (br, 1H),7.93 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.7 Hz, 1H), 7.12 (d, J=8.3 Hz, 1H),6.98 (dd, J=8.3, 2.7 Hz, 1H), 6.94 (d, J=8.7 Hz, 2H), 6.25 (s, 1H), 3.88(s, 3H), 3.86 (s, 3H), 2.82 (s, 2H), 1.34 (s, 6H).

EXAMPLE 60(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-bromophenyl)ethan-1-one

TLC: Rf0.62 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.83 (br, 1H),7.81 (d, J=8.4 Hz, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.32 (d, J=2.5 Hz, 1H),7.14 (d, J=8.3 Hz, 1H), 7.00 (dd, J=8.3, 2.5 Hz, 1H), 6.21 (s, 1H), 3.88(s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 60(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.99 (br, 1H),8.28 (d, J=8.7 Hz, 2H), 8.06 (d, J=8.7 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H),7.16 (d, J=8.5 Hz, 1H), 7.02 (dd, J=8.5, 2.6 Hz, 1H), 6.24 (s, 1H), 3.89(s, 3H), 2.86 (s, 2H), 1.38 (s, 6H).

EXAMPLE 60(7)(Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.69 (br, 1H),7.68 (d, J=8.8 Hz, 1H), 7.66 (dd, J=7.5, 2.1 Hz, 1H), 7.34 (m, 1H),7.02-6.93 (m, 2H), 6.81 (dd, J=8.8, 2.7 Hz, 1H), 6.70 (d, J=2.7 Hz, 1H),6.17 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 2.85 (s, 2H), 1.35 (s, 6H).

EXAMPLE 60(8)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-nitrophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.35 (br, 1H),7.86 (m, 1H), 7.64-7.59 (m, 3H), 7.54-7.47 (m, 1H), 7.27 (m, 1H), 7.22(m, 1H), 5.80 (s, 1H), 2.89 (s, 2H), 1.37 (s, 6H).

EXAMPLE 60(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-benzoyloxyphenyl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.81 (br, 1H),8.24-8.20 (m, 2H), 8.02 (d, J=9.0 Hz, 2H), 7.66 (m, 1H), 7.56-7.50 (m,2H), 7.34 (d, J=2.6 Hz, 1H), 7.30 (d, J=9.0 Hz, 2H), 7.14 (d, J=8.3 Hz,1H), 7.00 (dd, J=8.3, 2.6 Hz, 1H), 6.27 (s, 1H), 3.89 (s, 3H), 2.84 (s,2H), 1.36 (s, 6H).

EXAMPLE 60(10)(Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.69 (br, 1H),7.66 (dd, J=7.7, 2.0 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.43 (dd, J=8.3,2.0 Hz, 1H), 7.40-7.33 (m, 2H), 7.04-6.94 (m, 2H), 6.23 (s, 1H), 3.91(s, 3H), 2.68 (s, 2H), 1.35 (s, 6H).

EXAMPLE 60(11)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-nitrophenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.34 (br, 1H),7.87 (d, J=8.1 Hz, 1H), 7.64-7.60 (m, 2H), 7.51 (m, 1H), 7.38 (dd,J=9.6, 2.7 Hz, 1H), 7.22-7.10 (m, 2H), 5.78 (s, 1H), 2.88 (s, 2H), 1.37(s, 6H).

EXAMPLE 60(12)(Z)-2-(6-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.46 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.69 (br, 1H),7.66 (dd, J=7.7, 1.7 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.33 (m, 1H),7.01-6.93 (m, 2H), 6.47 (dd, J=8.6, 2.4 Hz, 1H), 6.34 (d, J=2.4 Hz, 1H),6.10 (s, 1H), 4.10 (m, 1H), 3.90 (s, 3H), 2.89 (d, J=3.0 Hz, 3H), 2.79(s, 2H), 1.35 (s, 6H).

EXAMPLE 60(13)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-nitrophenyl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.19 (br, 1H),7.89 (m, 1H), 7.66-7.59 (m, 2H), 7.52 (m, 1H), 7.06-6.99 (m, 2H), 6.90(d, J=8.4 Hz, 1H), 5.79 (s, 1H), 3.80 (s, 3H), 1.66 (s, 6H).

EXAMPLE 60(14)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylphenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.48-7.45 (m, 1H), 7.39 (dd, J=9.6, 2.7 Hz, 1H), 7.31-7.07 (m, 5H), 5.83(s, 1H), 2.87 (s, 2H), 2.51 (s, 3H), 1.37 (s, 6H).

EXAMPLE 60(15)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylphenyl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.63 (d, J=8.4 Hz, 1H), 7.46 (m, 1H), 7.30-7.17 (m, 5H), 5.85 (s, 1H),2.88 (s, 2H), 2.50 (s, 3H), 1.37 (s, 6H).

EXAMPLE 60(16)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methylphenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.38 (br, 1H),7.49-7.45 (m, 1H), 7.32-7.19 (m, 3H), 7.07 (d, J=2.9 Hz, 1H), 6.99 (dd,J=9.0, 2.9 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 5.85 (s, 1H), 3.80 (s, 3H),2.49 (s, 3H), 1.66 (s, 6H).

EXAMPLE 60(17)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-ethoxyphenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.51 (br, 1H),7.79 (dd, J=7.5, 1.8 Hz, 1H), 7.36 (m, 1H), 7.14 (d, J=3.0 Hz, 1H),7.05-6.93 (m, 3H), 6.88 (d, J=9.0 Hz, 1H), 6.51 (s, 1H), 4.15 (q, J=7.0Hz, 2H), 3.81 (s, 3H), 1.65 (s, 6H), 1.51 (t, J=7.0 Hz, 3H).

EXAMPLE 60(18)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-ethoxyphenyl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.60 (br, 1H),7.82 (dd, J=7.7, 1.7 Hz, 1H), 7.46 (dd, J=9.9, 2.4 Hz, 1H), 7.35 (m,1H), 7.19-7.06 (m, 2H), 7.01 (m, 1H), 6.95 (m, 1H), 6.52 (s, 1H), 4.16(q, J=7.0 Hz, 2H), 2.86 (s, 2H), 1.52 (t, J=7.0 Hz, 3H), 1.35 (s, 6H).

EXAMPLE 60(19)(Z)-2-(6,7-dimethoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 12.04 (s, 1H),8.15 (d, J=8.1 Hz, 2H), 7.91 (d, J=8.1 Hz, 2H), 7.49 (s, 1H), 6.93 (s,1H), 6.42 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 2.85 (s, 2H), 1.29 (s,6H).

EXAMPLE 60(20)(Z)-2-(6,7-dimethoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃) δ 11.64 (br s, 1H),7.66 (dd, J=7.5, 1.8 Hz, 1H), 7.39-7.33 (m, 1H), 7.20 (s, 1H), 7.04-6.95(m, 2H), 6.66 (s, 1H), 6.13 (s, 1H), 3.93 (s, 3H), 3.91 (s, 6H), 2.82(s, 2H), 1.36 (s, 6H).

EXAMPLE 60(21)(Z)-2-(7-cyclopentyloxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.70 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 12.05 (s, 1H),8.13 (d, J=8.1 Hz, 2H), 7.91 (d, J=8.1 Hz, 2H), 7.49 (s, 1H), 6.92 (s,1H), 6.36 (s, 1H), 5.05-5.00 (m, 1H), 3.82 (s, 3H), 2.85 (s, 2H),1.89-1.57 (m, 8H), 1.29 (s, 6H).

EXAMPLE 60(22)(Z)-2-(7-cyclopentyloxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 11.51 (s, 1H),7.56 (d, J=7.8 Hz, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.18 (s, 1H), 7.08 (d,J=7.8 Hz, 1H), 6.95 (t, J=7.8 Hz, 1H), 6.90 (s, 1H), 6.19 (s, 1H),4.86-4.82 (m, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 2.82 (s, 2H), 1.89-1.57(m, 8H), 1.27 (s, 6H).

EXAMPLE 60(23)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxycarbonylphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.36 (br, 1H),7.73 (m, 1H), 7.59 (m, 1H), 7.54-7.38 (m, 3H), 7.20-7.08 (m, 2H), 5.86(s, 1H), 3.86 (s, 3H), 2.87 (s, 2H), 1.36 (s, 6H).

EXAMPLE 60(24)(Z)-2-(6-cyclopentyloxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.94 (br, 1H),8.00 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.23 (s, 1H), 6.68 (s,1H), 6.12 (s, 1H), 4.85 (m, 1H), 3.93 (s, 3H), 2.83 (s, 2H), 2.05-1.78(m, 6H), 1.73-1.60 (m, 2H), 1.38 (s, 6H).

EXAMPLE 60(25)(Z)-2-(6-cyclopentyloxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.64 (br, 1H),7.66 (dd, J=7.7, 2.0 Hz, 1H), 7.35 (m, 1H), 7.20 (s, 1H), 7.03-7.94 (m,2H), 6.64 (s, 1H), 6.12 (s, 1H), 4.83 (m, 1H), 3.90 (s, 3H), 3.86 (s,3H), 2.80 (s, 2H), 2.05-1.77 (m, 6H), 1.70-1.56 (m, 2H), 1.35 (s, 6H).

EXAMPLE 60(26)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-nitrophenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 11.38 (s, 1H),7.87-7.83 (m, 2H), 7.73-7.60 (m, 2H), 7.44 (d, J=1.5 Hz, 1H), 7.25 (d,J=8.4 Hz, 1H), 7.10 (dd, J=8.4, 1.5 Hz, 1H), 6.16 (s, 1H), 3.81 (s, 3H),2.86 (s, 2H), 1.27 (s, 6H).

EXAMPLE 60(27)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-nitrophenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.95 (s, 1H),8.76 (m, 1H), 8.31-8.25 (m, 2H), 7.61 (t, J=8.1 Hz, 1H), 7.35 (d, J=2.4Hz, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.02 (dd, J=8.4, 2.4 Hz, 1H), 6.25 (s,1H), 3.90 (s, 3H), 2.86 (s, 2H), 1.38 (s, 6H).

EXAMPLE 60(28)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-cyanophenyl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.90 (br, 1H),8.21 (m, 1H), 8.16 (m, 1H), 7.72 (m, 1H), 7.55 (t, J=7.7 Hz, 1H), 7.32(d, J=2.4 Hz, 1H), 7.16 (d, J=8.2 Hz, 1H), 7.02 (dd, J=8.2, 2.4 Hz, 1H),6.19 (s, 1H), 3.90 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 60(29)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxycarbonylphenyl)ethan-1-one

TLC: Rf0.60 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.42 (br, 1H),7.72 (m, 1H), 7.61 (m, 1H), 7.50 (m, 1H), 7.43 (m, 1H), 7.23 (d, J=2.6Hz, 1H), 7.12 (d, J=8.3 Hz, 1H), 6.97 (dd, J=8.3, 2.6 Hz, 1H), 5.88 (s,1H), 3.85 (s, 3H), 3.83 (s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 61 EXAMPLE 61(2)

By the same procedure as described in example 1 using a correspondingderivative in place of the compound prepared in reference example 1 anda corresponding derivative in place of 2-methyl-1-phenylpropan-2-ol, thefollowing compounds of the present invention were given.

EXAMPLE 61(Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.67 (br, 1H),7.73 (dd, J=8.7, 5.7 Hz, 1H), 7.67 (d, J=7.8, 1.8 Hz, 1H), 7.36 (m, 1H),7.03-6.94 (m, 3H), 6.91 (dd, J=8.7, 2.7 Hz, 1H), 6.21 (s, 1H), 3.91 (s,3H), 2.88 (s, 2H), 1.36 (s, 6H).

EXAMPLE 61(1)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-ethoxyphenyl)ethan-1-one

TLC: Rf0.67 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.62 (br, 1H),7.80 (dd, J=7.5, 1.8 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.35 (ddd, J=8.4,7.5, 1.8 Hz, 1H), 7.28 (dd, J=8.3, 2.4 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H),7.01 (ddd, J=7.5, 7.5, 0.9 Hz, 1H), 6.94 (dd, J=8.4, 0.9 Hz, 1H), 6.51(s, 1H), 4.14 (q, J=7.0 Hz, 2H), 2.87 (s, 2H), 1.48 (t, J=7.0 Hz, 3H),1.36 (s, 6H).

EXAMPLE 61(2)(Z)-2-(7-methoxy-3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxycarbonylphenyl)ethan-1-one(compound A) and(Z)-2-(7-methoxy-3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-carboxyphenyl)ethan-1-one(compound B)

Compound A

TLC: Rf0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.91 (br, 1H),8.09 (d, J=8.6 Hz, 2H), 7.99 (d, J=8.6 Hz, 2H), 7.78 (d, J=8.6 Hz, 1H),6.95 (d, J=2.7 Hz, 1H), 6.84 (dd, J=8.6, 2.7 Hz, 1H), 6.23 (s, 1H), 3.94(s, 3H), 3.89 (s, 3H), 1.29 (br, 12H).

Compound B

TLC: Rf0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.89 (br, 1H),8.09 (d, J=8.4 Hz, 2H), 7.98 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.5 Hz, 1H),6.90 (d, J=2.4 Hz, 1H), 6.78 (dd, J=8.5, 2.4 Hz, 1H), 6.21 (s, 1H), 5.89(br, 1H), 3.94 (s, 3H), 1.27 (br, 12H).

EXAMPLE 62 EXAMPLE 62(5)

By the same procedure as described in example 14 using the compoundprepared in example 60(6), 60(8), 60(13), 60(11), 60(26) or 60(27), thefollowing compounds of the present invention were given.

EXAMPLE 62(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-aminophenyl)ethan-1-one

TLC: Rf0.70 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.66 (br, 1H),7.82 (d, J=9.0 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H), 7.12 (d, J=8.3 Hz, 1H),6.96 (dd, J=8.3, 2.6 Hz, 1H), 6.69 (d, J=9.0 Hz, 2H), 6.23 (s, 1H), 3.92(br, 2H), 3.88 (s, 3H), 2.81 (s, 2H), 1.33 (s, 6H).

EXAMPLE 62(1)(Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-aminophenyl)ethan-1-one

TLC: Rf0.43 (chloroform:methanol=10:1); NMR (DMSO-d₆): δ 8.11 (m, 1H),7.72-7.55 (m, 3H), 7.72-7.00 (br, 1H), 7.49-7.44 (m, 2H), 7.30 (m, 1H),6.01 (s, 1H), 3.32 (br, 2H), 2.71 (s, 2H), 1.22 (s, 6H).

EXAMPLE 62(2)(Z)-2-(7-methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-aminophenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.30 (br, 1H),7.68 (m, 1H), 7.19 (m, 1H), 7.17 (d, J=2.8 Hz, 1H), 6.99 (dd, J=8.8, 2.8Hz, 1H), 6.88 (d, J=8.8 Hz, 1H), 6.71-6.64 (m, 2H), 6.19 (s, 1H), 5.81(br, 2H), 3.85 (s, 3H), 1.64 (s, 6H).

EXAMPLE 62(3)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-aminophenyl)ethan-1-one

TLC: Rf0.47 (chloroform:methanol=5:1); NMR (CD₃OD): δ 8.29 (m, 1H),7.80-7.67 (m, 2H), 7.49-7.40 (m, 2H), 7.35 (dd, J=8.7, 2.8 Hz, 1H), 7.26(dt, J=8.7, 2.8 Hz, 1H), 6.37 (s, 1H), 2.82 (s, 2H), 1.29 (s, 6H).

EXAMPLE 62(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-aminophenyl)ethan-1-one

TLC: Rf0.28 (chloroform:methanol=5:1); NMR (CDCl₃): δ 8.43 (dd, J=8.4,1.2 Hz, 1H), 7.58 (m, 1H), 7.47 (m, 1H), 7.34 (m, 1H), 7.24 (d, J=8.4Hz, 1H), 7.11 (d, J=3.0 Hz, 1H), 7.00 (dd, J=8.4, 3.0 Hz, 1H), 6.36 (s,1H), 3.84 (s, 3H), 2.74 (br s, 2H), 1.80-1.40 (m, 3H), 1.40 (s, 6H).

EXAMPLE 62(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-aminophenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.79 (br s, 1H),7.33-7.26 (m, 3H), 7.21 (t, J=7.8 Hz, 1H), 7.12 (d, J=7.8 Hz, 1H), 6.98(dd, J=7.8, 2.7 Hz, 1H), 6.77 (m, 1H), 6.23 (s, 1H), 3.87 (s, 3H), 3.80(br s, 2H), 2.82 (s, 2H), 1.34 (s, 6H).

EXAMPLE 63(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-acetylaminophenyl)ethan-1-one

To a solution of the compound prepared in example 62 (0.33 g) inpyridine (0.25 ml) was added acetic anhydride (0.15 ml) at 0° C. and themixture was stirred for 1 hour at 0° C. To the reaction mixture wasadded water and was extracted with ethyl acetate. The extract was washedwith 1N hydrochloric acid, water and brine, dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=3:1→1:1) to give thecompound of the present invention (0.23 g) having the following physicaldata.

TLC: Rf0.35 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.79 (br, 1H),7.93 (d, J=8.9 Hz, 2H), 7.57 (d, J=8.9 Hz, 2H), 7.33 (d, J=2.5 Hz, 1H),7.13 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.5 Hz, 1H), 6.25 (s, 1H), 3.88(s, 3H), 2.83 (s, 2H), 2.21 (s, 3H), 1.56 (br, 1H), 1.34 (s, 6H).

EXAMPLE 63(1)-EXAMPLE 63(37)

By the same procedure as described in example 63 using the compoundprepared in example 62, or the compound prepared in 62(4) or 62(5)instead, and acetic anhydride or a corresponding acid anhydride orsulfonyl halide, optionally followed by converting to a correspondingsalt by a conventional method, the following compounds of the presentinvention were given.

EXAMPLE 63(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((cyclohexylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.64 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.79 (br, 1H),7.93 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.34 (d, J=2.6 Hz, 1H),7.24 (br, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 2.6 Hz, 1H),6.26 (s, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 2.25 (m, 1H), 2.02-1.94 (m,2H), 1.90-1.82 (m, 2H), 1.75-1.67 (m, 1H), 1.64-1.49 (m, 3H), 1.34 (s,6H), 1.40-1.25 (m, 2H).

EXAMPLE 63(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((methoxycarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (br s, 1H),7.93 (d, J=8.7 Hz, 2H), 7.45 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.7 Hz, 1H),7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 2.7 Hz, 1H), 6.73 (s, 1H), 6.25(s, 1H), 3.88 (s, 3H), 3.80 (s, 3H), 2.83 (s, 2H), 1.34 (s, 6H).

EXAMPLE 63(3)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-mesylaminophenyl)ethan-1-one

free compound:

TLC: Rf0.35 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.80 (br s, 1H),7.95 (d, J=8.7 Hz, 2H), 7.32 (d, J=2.7 Hz, 1H), 7.25 (d, J=8.7 Hz, 2H),7.14 (d, J=8.1 Hz, 1H), 7.00 (dd, J=8.1, 2.7 Hz, 1H), 6.60 (s, 1H), 6.22(s, 1H), 3.88 (s, 3H), 3.06 (s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

Sodium Salt:

TLC: Rf0.35 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 11.62 (s, 1H),7.68 (d, J=8.7 Hz, 2H), 7.44 (d, J=2.7 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H),7.02 (dd, J=8.4, 2.7 Hz, 1H), 6.76 (d, J=8.7 Hz, 2H), 6.30 (s, 1H), 3.84(s, 3H), 2.78 (s, 2H), 2.57 (s, 3H), 1.23 (s, 6H).

EXAMPLE 63(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-acetylaminophenyl)ethan-1-one

TLC: Rf0.62 (chloroform:methanol=5:1); NMR (DMSO-d₆): δ 11.80 (s, 1H),8.10 (d, J=8.1 Hz, 1H), 7.68-7.58 (m, 2H), 7.32 (m, 1H), 7.24-7.20 (m,2H), 7.05 (dd, J=8.7, 2.7 Hz, 1H), 6.97 (d, J=2.7 Hz, 1H), 5.97 (s, 1H),3.78 (s, 3H), 3.09 (s, 2H), 1.71 (s, 3H), 0.96 (s, 6H).

EXAMPLE 63(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-acetylaminophenyl)ethan-1-one

TLC: Rf0.45 (ethyl acetate); NMR (CDCl₃): δ 11.81 (br s, 1H), 7.91 (d,J=8.4 Hz, 1H), 7.80 (s, 1H), 7.66 (d, J=7.5 Hz, 1H), 7.42-7.37 (m, 2H),7.33 (d, J=2.7 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.99 (dd, J=8.4, 2.7 Hz,1H), 6.24 (s, 1H), 3.88 (s, 3H), 2.83 (s, 2H), 2.20 (s, 3H), 1.35 (s,6H).

EXAMPLE 63(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-formylaminophenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.81 (br, 1H),8.80 (d, J=11.6 Hz, 1H*1:2), 8.43 (d, J=1.8 Hz, 1H*1:2), 7.96 (d, J=9.0Hz, 2H*1:2), 7.95 (d, J=9.0 Hz, 2H*1:2), 7.62 (d, J=9.0 Hz, 2H*1:2),7.43 (d, J=11.6 Hz, 1H*1:2), 7.33 (d, J=2.4 Hz, 1H), 7.22 (br, 1H*1:2),7.16-7.10 (m, 1H+2H*1:2), 6.99 (m, 1H), 6.25 & 6.27 (s, 1H), 3.88 (s,3H), 2.83 (s, 2H), 1.36 & 1.35 (s, 6H).

EXAMPLE 63(7)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-((2-carboxybenzoyl)amino)phenyl)ethan-1-one

TLC: Rf0.28 (chloroform:methanol=5:1); NMR (DMSO-d₆): δ 11.85 (s, 1H),8.10 (d, J=8.1 Hz, 1H), 7.75-7.71 (m, 2H), 7.65-7.63 (m, 2H), 7.58-7.44(m, 3H), 7.36-7.31 (m, 2H), 7.09 (dd, J=8.4, 2.7 Hz, 1H), 6.99 (d, J=2.7Hz, 1H), 6.00 (s, 1H), 3.87 (s, 3H), 3.31 (m, 1H), 3.23 (s, 2H), 1.04(s, 6H).

EXAMPLE 63(8)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-carboxybenzoyl)amino)phenyl)ethan-1-one

TLC: Rf0.45 (chloroform:methanol=5:1); NMR (DMSO-d₆): δ 11.83 (s, 1H),10.42 (s, 1H), 8.22 (s, 1H), 7.89-7.83 (m, 2H), 7.75-7.56 (m, 4H),7.45-7.38 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.10 (dd, J=8.4, 2.4 Hz, 1H),6.35 (s, 1H), 3.83 (s, 3H), 3.32 (m, 1H), 2.85 (s, 2H), 1.28 (s, 6H).

EXAMPLE 63(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-carboxybenzoyl)amino)phenyl)ethan-1-one

TLC: Rf0.42 (chloroform:methanol=5:1); NMR (DMSO-d₆): δ 11.86 (s, 1H),10.53 (s, 1H), 8.01 (d, J=8.7 Hz, 2H), 7.89 (m, 1H), 7.76 (d, J=8.7 Hz,2H), 7.69-7.53 (m, 4H), 7.24 (d, J=8.4 Hz, 1H), 7.08 (dd, J=8.4, 2.7 Hz,1H), 6.43 (s, 1H), 3.86 (s, 3H), 3.32 (m, 1H), 2.83 (s, 2H), 1.27 (s,6H).

EXAMPLE 63(10)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((furan-2-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.86 (br, 1H),8.18 (br, 1H), 8.08 (m, 1H), 7.92 (t, J=1.8 Hz, 1H), 7.71 (dt, J=7.8,1.8 Hz, 1H), 7.54 (dd, J=1.9, 0.9 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.36(d, J=2.7 Hz, 1H), 7.26 (dd, J=3.4, 0.9 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H),7.00 (dd, J=8.1, 2.7 Hz, 1H), 6.58 (dd, J=3.4, 1.9 Hz, 1H), 6.28 (s,1H), 3.89 (s, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 63(11)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,4-dimethoxybenzoylamino)phenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.86 (br, 1H),8.14 (m, 1H), 7.97 (br, 1H), 7.91 (t, J=1.8 Hz, 1H), 7.71 (dt, J=8.1,1.8 Hz, 1H), 7.51 (d, J=1.9 Hz, 1H), 7.46 (t, J=8.1 Hz, 1H), 7.42 (dd,J=8.2, 1.9 Hz, 1H), 7.35 (d, J=2.7 Hz, 1H), 7.14 (d, J=8.5 Hz, 1H), 6.99(dd, J=8.5, 2.7 Hz, 1H), 6.93 (d, J=8.2 Hz, 1H), 6.29 (s, 1H), 3.97 (s,3H), 3.94 (s, 3H), 3.88 (s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 63(12)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.36 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.86 (br, 1H),8.37 (br, 1H), 7.99 (m, 1H), 7.86 (t, J=1.8 Hz, 1H), 7.69 (dt, J=7.9,1.8 Hz, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 7.14 (d,J=8.5 Hz, 1H), 6.99 (dd, J=8.5, 2.5 Hz, 1H), 6.26 (s, 1H), 4.04 (s, 2H),3.86 (s, 3H), 3.53 (s, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 63(13)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((furan-2-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.63 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.81 (br, 1H),8.18 (br, 1H), 7.98 (d, J=8.7 Hz, 2H), 7.74 (d, J=8.7 Hz, 2H), 7.54 (dd,J=1.7, 0.8 Hz, 1H), 7.35 (d, J=2.6 Hz, 1H), 7.27 (dd, J=3.5, 0.8 Hz,1H), 7.14 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.6 Hz, 1H), 6.58 (dd,J=3.5, 1.7 Hz, 1H), 6.28 (s, 1H), 3.89 (s, 3H), 2.83 (s, 2H), 1.35 (s,6H).

EXAMPLE 63(14)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,4-dimethoxybenzoylamino)phenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.82 (br, 1H),7.99 (d, J=8.6 Hz, 2H), 7.88 (br, 1H), 7.72 (d, J=8.6 Hz, 2H), 7.52 (d,J=2.0 Hz, 1H), 7.41 (dd, J=8.4, 2.0 Hz, 1H), 7.36 (d, J=2.5 Hz, 1H),7.14 (d, J=8.6 Hz, 1H), 6.99 (dd, J=8.6, 2.5 Hz, 1H), 6.93 (d, J=8.4 Hz,1H), 6.29 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.89 (s, 3H), 2.84 (s,2H), 1.35 (s, 6H).

EXAMPLE 63(15)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-methoxyphenyl)acetyl)amino)phenyl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.79 (br, 1H),7.89 (d, J=8.9 Hz, 2H), 7.49 (d, J=8.9 Hz, 2H), 7.32 (d, J=2.4 Hz, 1H),7.26 (d, J=8.6 Hz, 2H), 7.17 (br, 1H), 7.12 (d, J=8.4 Hz, 1H), 6.98 (dd,J=8.4, 2.4 Hz, 1H), 6.95 (d, J=8.6 Hz, 2H), 6.23 (s, 1H), 3.88 (s, 3H),3.84 (s, 3H), 3.71 (s, 2H), 2.82 (s, 2H), 1.33 (s, 6H).

EXAMPLE 63(16)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.81 (br, 1H),8.36 (br, 1H), 7.95 (d, J=8.7 Hz, 2H), 7.66 (d, J=8.7 Hz, 2H), 7.34 (d,J=2.5 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 6.99 (d, J=8.2, 2.5 Hz, 1H), 6.26(s, 1H), 4.04 (s, 2H), 3.89 (s, 3H), 3.52 (s, 3H), 2.83 (s, 2H), 1.35(s, 6H).

EXAMPLE 63(17)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,5-dimethoxybenzoylamino)phenyl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.82 (br, s,1H), 7.99 (d, J=8.7 Hz, 2H), 7.90 (br, s, 1H), 7.72 (d, J=8.7 Hz, 2H),7.35 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.05-6.90 (m, 3H), 6.63(t, J=2.1 Hz, 1H), 6.28 (s, 1H), 3.89 (s, 3H), 3.86 (s, 6H), 2.83 (s,2H), 1.35 (s, 6H).

EXAMPLE 63(18)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-3-(2-chlorophenyl)isooxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.70 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.76 (br, s,1H), 7.84 (d, J=8.7 Hz, 2H), 7.70-7.50 (m, 4H), 7.30 (d, J=2.7 Hz, 1H),7.20 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.4 Hz, 1H), 7.03 (br, s, 1H), 6.98(dd, J=8.4, 2.7 Hz, 1H), 6.20 (s, 1H), 3.87 (s, 3H), 2.86 (s, 3H), 2.82(s, 2H), 1.33 (s, 6H).

EXAMPLE 63(19)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-chlorophenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.83 (br, s,1H), 9.82 (br, s, 1H), 8.72 (dd, J=7.5, 2.1 Hz, 1H), 8.26 (dd, J=4.5,2.1 Hz, 1H), 7.98 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.47 (d,J=9.0 Hz, 2H), 7.34 (d, J=2.4 Hz, 1H), 7.30-7.15 (m, 1H), 7.21 (d, J=9.0Hz, 2H), 7.13 (d, J=8.4 Hz, 1H), 6.99 (dd, J=8.4, 2.4 Hz, 1H), 6.28 (s,1H), 3.89 (s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 63(20)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methylbutanoyl)amino)phenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.79 (br, s,1H), 7.93 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.7 Hz, 2H), 7.33 (d, J=3.0 Hz,1H), 7.28 (br, s, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 3.0 Hz,1H), 6.25 (s, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 2.28-2.20 (m, 3H), 1.34(s, 6H), 1.03 (d, J=6.6 Hz, 6H).

EXAMPLE 63(21)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methylthiopropanoyl)amino)phenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.80 (br, 1H),7.94 (d, J=8.3 Hz, 2H), 7.69 (br, 1H), 7.60 (d, J=8.3 Hz, 2H), 7.33 (d,J=2.4 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 6.99 (dd, J=8.0, 2.4 Hz, 1H),6.25 (s, 1H), 3.88 (s, 3H), 2.91 (t, J=7.0 Hz, 2H), 2.83 (s, 2H), 2.68(t, J=7.0 Hz, 2H), 2.18 (s, 3H), 1.34 (s, 6H).

EXAMPLE 63(22)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,5-dimethoxybenzoylamino)phenyl)ethan-1-one

TLC: Rf0.59 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.86 (br, s,1H), 8.09 (m, 1H), 7.94 (br, s, 1H), 7.91 (t, J=2.1 Hz, 1H), 7.72 (m,1H), 7.46 (t, J=8.1 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.7 Hz,1H), 7.05-6.95 (m, 1H), 7.01 (d, J=2.4 Hz, 2H), 6.63 (t, J=2.4 Hz, 1H),6.27 (s, 1H), 3.88 (s, 3H), 3.86 (s, 6H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 63(23)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-3-(2-chlorophenyl)isooxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.64 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.73 (br, s,1H), 7.70-7.50 (m, 6H), 7.40-7.30 (m, 2H), 7.33 (d, J=2.1 Hz, 1H), 7.15(d, J=8.1 Hz, 1H), 7.01 (dd, J=8.1, 2.1 Hz, 1H), 7.00-6.95 (br, 1H),6.13 (s, 1H), 3.90 (s, 3H), 2.85 (s, 3H), 2.83 (s, 2H), 1.35 (s, 6H).

EXAMPLE 63(24)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-chlorophenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.63 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.81 (br, s,1H), 9.75 (br, s, 1H), 8.73 (dd, J=7.8, 1.8 Hz, 1H), 8.26 (dd, J=4.5,1.8 Hz, 1H), 8.16 (m, 1H), 7.90 (t, J=1.8 Hz, 1H), 7.71 (dt, J=7.5, 1.8Hz, 1H), 7.50-7.40 (m, 1H), 7.46 (d, J=9.0 Hz, 2H), 7.32 (d, J=2.7 Hz,1H), 7.30-7.10 (m, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.14 (d, J=8.1 Hz, 1H),6.99 (dd, J=8.1, 2.7 Hz, 1H), 6.26 (s, 1H), 3.87 (s, 3H), 2.83 (s, 2H),1.34 (s, 6H).

EXAMPLE 63(25)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methylbutanoyl)amino)phenyl)ethan-1-one

TLC: Rf0.70 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 11.82 (br, s,1H), 7.96 (m, 1H), 7.79 (t, J=1.8 Hz, 1H), 7.66 (m, 1H), 7.40 (t, J=8.1Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.26 (br, s, 1H), 7.14 (d, J=8.1 Hz,1H), 6.99 (dd, J=8.1, 2.4 Hz, 1H), 6.25 (s, 1H), 3.88 (s, 3H), 2.83 (s,2H), 2.30-2.20 (m, 3H), 1.35 (s, 6H), 1.03 (d, J=6.6 Hz, 6H).

EXAMPLE 63(26)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-2-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.88 (s, 1H),10.17 (s, 1H), 8.65 (m, 1H), 8.32 (d, J=7.8 Hz, 1H), 8.19 (m, 1H), 8.08(m, 1H), 7.92 (dt, J=1.5, 7.8 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.52-7.45(m, 2H), 7.38 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd,J=8.4, 2.4 Hz, 1H), 6.30 (s, 1H), 3.90 (s, 3H), 2.84 (s, 2H), 1.37 (s,6H).

EXAMPLE 63(27)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.27 (ethyl acetate); NMR (CDCl₃): δ 11.79 (s, 1H), 9.18 (d,J=1.8 Hz, 1H), 8.76 (dd, J=4.5, 1.8 Hz, 1H), 8.58 (s, 1H), 8.25 (dt,J=8.1, 1.8 Hz, 1H), 8.14 (d, J=8.1 Hz, 1H), 7.97 (m, 1H), 7.74 (d, J=8.1Hz, 1H), 7.50-7.43 (m, 2H), 7.31 (d, J=2.4 Hz, 1H), 7.12 (d, J=8.1 Hz,1H), 6.99 (dd, J=8.1, 2.4 Hz, 1H), 6.24 (s, 1H), 3.87 (s, 3H), 2.77 (s,2H), 1.27 (s, 6H).

EXAMPLE 63(28)(Z)-2-(7-methoxy-3,3-dimethyl-3′,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.24 (ethyl acetate); NMR (CDCl₃): δ 11.81 (s, 1H), 8.79 (d,J=6.0 Hz, 2H), 8.30 (s, 1H), 8.11 (d, J=7.8 Hz, 1H), 8.01 (s, 1H),7.75-7.71 (m, 3H), 7.47 (t, J=7.8 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.14(d, J=8.1 Hz, 1H), 7.00 (dd, J=8.1, 2.4 Hz, 1H), 6.27 (s, 1H), 3.88 (s,3H), 2.81 (s, 2H), 1.31 (s, 6H).

EXAMPLE 63(29)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((ethoxycarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.62 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (s, 1H),7.72 (m, 2H), 7.62 (d, J=8.1 Hz, 1H), 7.38 (t, J=8.1 Hz, 1H), 7.33 (d,J=2.4 Hz, 1H), 7.13 (d, J=8.1 Hz, 1H), 6.99 (dd, J=8.1, 2.4 Hz, 1H),6.67 (s, 1H), 6.24 (s, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.88 (s, 3H), 2.83(s, 2H), 1.35 (s, 6H), 1.33 (t, J=7.2 Hz, 3H).

EXAMPLE 63(30)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((isopropyloxycarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.68 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.80 (s, 1H),7.72 (m, 2H), 7.61 (d, J=8.1 Hz, 1H), 7.38 (t, J=8.1 Hz, 1H), 7.33 (d,J=2.4 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.99 (dd, J=8.4, 2.4 Hz, 1H),6.60 (s, 1H), 6.24 (s, 1H), 5.03 (m, 1H), 3.88 (s, 3H), 2.83 (s, 2H),1.35 (s, 6H), 1.31 (d, J=6.3 Hz, 6H).

EXAMPLE 63(31)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-2-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.83 (s, 1H),10.17 (s, 1H), 8.64 (m, 1H), 8.32 (m, 1H), 8.01 (d, J=8.4 Hz, 2H), 7.93(dt, J=1.5, 7.8 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.50 (m, 1H), 7.36 (d,J=2.7 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.99 (dd, J=8.4, 2.7 Hz, 1H),6.30 (s, 1H), 3.90 (s, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 63(32)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.43 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.82 (s, 1H),9.12 (d, J=1.8 Hz, 1H), 8.79 (dd, J=4.8, 1.8 Hz, 1H), 8.23 (dt, J=8.1,1.8 Hz, 1H), 8.09 (s, 1H), 7.99 (d, J=9.0 Hz, 2H), 7.46 (dd, J=8.1, 4.8Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd,J=8.4, 2.4 Hz, 1H), 6.28 (s, 1H), 3.89 (s, 3H), 2.83 (s, 2H), 1.35 (s,6H).

EXAMPLE 63(33)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((ethoxycarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (s, 1H),7.92 (d, J=8.7 Hz, 2H), 7.45 (d, J=8.7 Hz, 2H), 7.33 (d, J=2.7 Hz, 1H),7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 2.7 Hz, 1H), 6.72 (s, 1H), 6.25(s, 1H), 4.25 (q, J=7.2 Hz, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 1.34 (s,6H), 1.32 (t, J=7.2 Hz, 3H).

EXAMPLE 63(34)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((isopropyloxycarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.77 (s, 1H),7.92 (d, J=8.7 Hz, 2H), 7.45 (d, J=8.7 Hz, 2H), 7.33 (d, J=2.4 Hz, 1H),7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 2.4 Hz, 1H), 6.68 (s, 1H), 6.25(s, 1H), 5.04 (m, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 1.34 (s, 6H), 1.31(d, J=6.0 Hz, 6H).

EXAMPLE 63(35)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.48 (chloroform:methanol=9:1); NMR (CDCl₃): δ 11.83 (s, 1H),8.82 (d, J=9.0 Hz, 2H), 8.01-7.99 (m, 3H), 7.75-7.72 (m, 4H), 7.35 (d,J=2.4 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.00 (dd, J=8.1, 2.4 Hz, 1H),6.28 (s, 1H), 3.89 (s, 3H), 2.84 (s, 2H), 1.35 (s, 6H).

EXAMPLE 63(36)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclopropylcarbonylamino)phenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.81 (s, 1H),7.94 (m, 1H), 7.80 (m, 1H), 7.65 (m, 1H), 7.50 (m, 1H), 7.39 (t, J=8.1Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.13 (d, J=8.1 Hz, 1H), 6.99 (dd,J=8.1, 2.7 Hz, 1H), 6.25 (s, 1H), 3.88 (s, 3H), 2.83 (s, 2H), 1.53 (m,1H), 1.35 (s, 6H), 1.11 (m, 2H), 0.87 (m, 2H).

EXAMPLE 63(37)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclopropylcarbonylamino)phenyl)ethan-1-one

TLC: Rf0.32 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.79 (s, 1H),7.93 (d, J=8.4 Hz, 2H), 7.59 (d, J=8.4 Hz, 2H), 7.49 (s, 1H), 7.34 (d,J=2.7 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4, 2.7 Hz, 1H),6.26 (s, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 1.54 (m, 1H), 1.34 (s, 6H),1.12 (m, 2H), 0.88 (m, 2H).

EXAMPLE 64(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-cyclohexylcarbonyl-N-methylamino)phenyl)ethan-1-one

To a solution of the compound prepared in example 63(1) (0.28 g) inN,N-dimethylformamide (3 ml) was added sodium hydride under cooling withice, and the mixture was stirred for 1 hour. To the reaction mixture wasadded methyl iodide (97.1 μl) and the mixture was stirred overnight atroom temperature. To the reaction mixture was added a saturated aqueoussolution of ammonium chloride and was extracted with ethyl acetate. Theextract was washed with water and a saturated aqueous solution of sodiumchloride successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=3:1→2:1) to give the compound of thepresent invention (0.20 g) having the following physical data.

TLC: Rf0.51 (hexane:acetone=2:1); NMR (CDCl₃): δ 11.87 (br, 1H), 7.98(d, J=8.3 Hz, 2H), 7.34 (d, J=2.6 Hz, 1H), 7.23 (d, J=8.3 Hz, 2H), 7.15(d, J=8.2 Hz, 1H), 7.01 (dd, J=8.2, 2.6 Hz, 1H), 6.27 (s, 1H), 3.88 (s,3H), 3.27 (s, 3H), 2.85 (s, 2H), 2.24 (m, 1H), 1.68-1.64 (m, 4H),1.60-1.47 (m, 3H), 1.37 (s, 6H), 1.16 (m, 1H), 1.08-0.88 (m, 2H).

EXAMPLE 65-EXAMPLE 65(2)

By the same procedure as described in example 13 using the compoundprepared in example 60, 60(5) or 60(10) in place of the compoundprepared in example 12, the following compounds of the present inventionwere given.

EXAMPLE 65(Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.62 (br, 1H),10.03 (s, 1H), 8.25 (d, J=1.4 Hz, 1H), 7.92 (dd, J=7.8, 1.8 Hz, 1H),7.68 (dd, J=7.7, 1.4 Hz, 1H), 7.39 (m, 1H), 7.38 (d, J=7.7 Hz, 1H),7.05-6.97 (m, 2H), 6.38 (s, 1H), 3.93 (s, 3H), 2.98 (s, 2H), 1.37 (s,6H).

EXAMPLE 65(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-formylphenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.97 (br, 1H),10.08 (s, 1H), 8.07 (d, J=8.3 Hz, 2H), 7.95 (d, J=8.3 Hz, 2H), 7.34 (d,J=2.5 Hz, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4, 2.5 Hz, 1H),6.28 (s, 1H), 3.89 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 65(2)(Z)-2-(6-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.58 (br, 1H),10.05 (s, 1H), 7.91 (d, J=8.0 Hz, 1H), 7.80 (dd, J=8.0, 1.7 Hz, 1H),7.72 (d, J=1.7 Hz, 1H), 7.68 (dd, J=7.5, 1.8 Hz, 1H), 7.38 (m, 1H),7.05-6.96 (m, 2H), 6.36 (s, 1H), 3.92 (s, 3H), 2.98 (s, 2H), 1.37 (s,6H).

EXAMPLE 66-EXAMPLE 66(2)

By the same procedure as described in example 15 using the compoundprepared in example 60, 60(5) or 60(10) in place of the compoundprepared in example 12, the following compounds of the present inventionwere given.

EXAMPLE 66(Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.55 (ethyl acetate:methanol=20:1); NMR (CDCl₃): δ 11.62 (br,1H), 8.49 (d, J=1.8 Hz, 1H), 8.12 (dd, J=7.8, 1.8 Hz, 1H), 7.67 (dd,J=7.8, 1.5 Hz, 1H), 7.38 (m, 1H), 7.31 (d, J=7.8 Hz, 1H), 7.05-6.96 (m,2H), 6.40 (s, 1H), 3.93 (s, 3H), 2.96 (s, 2H), 2.64 (br, 1H), 1.37 (s,6H).

EXAMPLE 66(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-carboxyphenyl)ethan-1-one

TLC: Rf0.39 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.96 (br, 1H),8.17 (d, J=8.7 Hz, 2H), 8.01 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.5 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.5 Hz, 1H), 6.28 (s, 1H), 3.89(s, 3H), 3.12 (br, 1H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 66(2)(Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.58 (ethyl acetate:methanol=20:1); NMR (CDCl₃): δ 11.61 (br,1H), 8.03 (dd, J=8.3, 1.7 Hz, 1H), 7.94 (d, J=1.7, 1H), 7.84 (d, J=8.3Hz, 1H), 7.69 (dd, J=7.5, 1.8 Hz, 1H), 7.38 (m, 1H), 7.05-6.96 (m, 2H),6.35 (s, 1H), 5.03 (br, 1H), 3.92 (s, 3H), 2.96 (s, 2H), 1.37 (s, 6H).

EXAMPLE 67-EXAMPLE 67(1)

By the same procedure as described in example 4 using the compoundprepared in example 60(23) or 60(29) in place of the compound preparedin example 1(1), the following compounds of the present invention weregiven.

EXAMPLE 67(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-carboxyphenyl)ethan-1-one

TLC: Rf0.74 (ethyl acetate:methanol=20:1); NMR (CDCl₃): δ 11.58 (br,1H), 8.26 (m, 1H), 7.72 (m, 1H), 7.59-7.54 (m, 2H), 7.46 (dd, J=9.5, 2.3Hz, 1H), 7.28-7.20 (m, 2H), 6.01 (s, 1H), 2.93 (s, 2H), 1.28 (s, 6H).

EXAMPLE 67(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-carboxyphenyl)ethan-1-one

TLC: Rf0.54 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.64 (br, 1H),8.27 (m, 1H), 7.72 (m, 1H), 7.60-7.50 (m, 2H), 7.26 (d, J=2.7 Hz, 1H),7.18 (d, J=8.4 Hz, 1H), 7.05 (dd, J=8.4, 2.7 Hz, 1H), 6.04 (s, 1H), 3.86(s, 3H), 2.87 (s, 2H), 1.55 (br, 1H), 1.40 (s, 6H).

EXAMPLE 68(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-((2-hydroxy-1,1-dimethylethyl)carbamoyl)phenyl)ethan-1-one

To a solution of the compound prepare in example 66(1) (0.3 g) inN,N-dimethylformamide (4.0 ml) were added 1-hydroxybenzotriazole (0.12g), N-methylmorpholine (0.14 ml), 2-hydroxy-1,1-dimethylethylamine (0.12ml) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride(0.25 g) and the mixture was stirred for 4 hours at room temperature. Tothe reaction mixture was added water and was extracted with ethylacetate. The extract was washed with 1N hydrochloric acid, a saturatedaqueous solution of sodium bicarbonate and brine successively, driedover anhydrous magnesium sulfate and concentrated to give the compoundof the present invention (0.35 g) having the following physical data.

TLC: Rf0.54 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.93 (br, 1H),7.98 (d, J=8.3 Hz, 2H), 7.79 (d, J=8.3 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.00 (dd, J=8.3, 2.6 Hz, 1H), 6.29 (br, 1H),6.26 (s, 1H), 4.72 (br, 1H), 3.88 (s, 3H), 3.72 (s, 2H), 2.84 (s, 2H),1.44 (s, 6H), 1.36 (s, 6H).

EXAMPLE 68(1)-EXAMPLE 68(9)

By the same procedure as described in example 68 using the compoundprepared in example 66(1) or example 66, 66(2), 67 or 67(1) and acorresponding derivative in place of 2-hydroxy-1,1-dimethylethylamine,the following compounds of the present invention were given.

EXAMPLE 68(1)(Z)-2-(7-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.73 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.61 (br, 1H),8.20 (d, J=1.5 HZ, 1H), 7.83 (dd, J=7.8, 1.8 Hz, 1H), 7.65 (dd, J=7.5,1.5 Hz, 1H), 7.37 (m, 1H), 7.30 (d, J=7.5 Hz, 1H), 7.04-6.95 (m, 2H),6.31 (s, 1H), 6.20-5.50 (br, 2H), 3.92 (s, 3H), 2.95 (s, 2H), 1.36 (s,6H).

EXAMPLE 68(2)(Z)-2-(6-carbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.66 (ethyl acetate:methanol=20:1); NMR (CDCl₃): δ 11.59 (br,1H), 7.81 (d, J=8.7 Hz, 1H), 7.71-7.65 (m, 3H), 7.38 (m, 1H), 7.05-6.95(m, 2H), 6.31 (s, 1H), 6.10 (br, 1H), 5.70 (br, 1H), 3.92 (s, 3H), 2.94(s, 2H), 1.36 (s, 6H).

EXAMPLE 68(3)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-carbamoylphenyl)ethan-1-one

TLC: Rf0.45 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.50 (br, 1H),7.79 (m, 1H), 7.56-7.38 (m, 4H), 7.22-7.10 (m, 2H), 7.04 (br, 1H), 5.88(s, 1H), 5.63 (br, 1H), 2.88 (s, 2H), 1.37 (s, 6H).

EXAMPLE 68(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyclohexylcarbamoylphenyl)ethan-1-one

TLC: Rf0.51 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.92 (br, 1H),7.98 (d, J=8.6 Hz, 2H), 7.81 (d, J=8.6 Hz, 2H), 7.33 (d, J=2.5 Hz, 1H),7.15 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.5 Hz, 1H), 6.27 (s, 1H), 6.00(d, J=7.5 Hz, 1H), 4.00 (m, 1H), 3.89 (s, 3H), 2.84 (s, 2H), 2.10-2.03(m, 2H), 1.82-1.72 (m, 2H), 1.72-1.60 (m, 1H), 1.60-1.15 (m, 5H), 1.36(s, 6H).

EXAMPLE 68(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-cyclohexyl-N-methylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.87 (br, 1H),7.96 (d, J=7.8 Hz, 2H), 7.42 (d, J=7.8 Hz, 2H), 7.34 (d, J=2.5 Hz, 1H),7.14 (d, J=8.3 Hz, 1H), 7.00 (dd, J=8.3, 2.5 Hz, 1H), 6.27 (s, 1H), 4.55(m, 1*0.36H), 3.88 (s, 3H), 3.45 (m, 1*0.64H), 2.98 (s, 3*0.64H), 2.84(s, 2H), 2.80 (s, 3*0.36H), 1.90-1.62 (m, 5H), 1.62-1.36 (m, 3H), 1.36(s, 6H), 1.17-0.96 (m, 2H).

EXAMPLE 68(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methylcarbamoylphenyl)ethan-1-one

TLC: Rf0.54 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.91 (br, 1H),7.98 (d, J=8.6 Hz, 2H), 7.82 (d, J=8.6 Hz, 2H), 7.34 (d, J=2.6 Hz, 1H),7.15 (d, J=8.2 Hz, 1H), 7.00 (dd, J=8.2, 2.6 Hz, 1H), 6.27 (s, 1H), 6.21(br, 1H), 3.89 (s, 3H), 3.04 (d, J=4.8 Hz, 3H), 2.84 (s, 2H), 1.36 (s,6H).

EXAMPLE 68(7)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydrazinocarbonylphenyl)ethan-1-one

TLC: Rf0.32 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.91 (br, 1H),7.99 (d, J=8.1 Hz, 2H), 7.81 (d, J=8.1 Hz, 2H), 7.58 (br, 1H), 7.33 (d,J=2.2 Hz, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4, 2.2 Hz, 1H),6.26 (s, 1H), 4.31 (br, 2H), 3.88 (s, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 68(8)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-carbamoylphenyl)ethan-1-one

TLC: Rf0.46 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.56 (br, 1H),7.82 (m, 1H), 7.55-7.44 (m, 3H), 7.25 (br, 1H), 7.20 (d, J=2.6 Hz, 1H),7.13 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.6 Hz, 1H), 5.89 (s, 1H), 5.65(br, 1H), 3.82 (s, 3H), 2.85 (s, 2H), 1.36 (s, 6H).

EXAMPLE 68(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-carbamoylphenyl)ethan-1-one

TLC: Rf0.39 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.93 (br, 1H),8.01 (d, J=8.7 Hz, 2H), 7.88 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.5 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.5 Hz, 1H), 6.27 (s, 1H), 6.12(br, 1H), 5.65 (br, 1H), 3.89 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 69 EXAMPLE 69(1)

By the same procedure as described in example 28 using the compoundprepared in example 65 and example 65(1) in place of the compoundprepared in example 13 the following compounds of the present inventionwere given.

EXAMPLE 69(Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.65 (br, 1H),7.74 (d, J=1.7 Hz, 1H), 7.65 (dd, J=7.5, 1.7 Hz, 1H), 7.41 (dd, J=7.7,1.7 Hz, 1H), 7.36 (m, 1H), 7.19 (d, J=7.7 Hz, 1H), 7.03-6.94 (m, 2H),6.25 (s, 1H), 4.71 (d, J=4.8 Hz, 2H), 3.91 (s, 3H), 2.88 (s, 2H), 1.83(t, J=4.8 Hz, 1H), 1.35 (s, 6H).

EXAMPLE 69(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydroxymethylphenyl)ethan-1-one

TLC: Rf0.62 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.83 (br, 1H),7.94 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.6 Hz, 2H), 7.34 (d, J=2.6 Hz, 1H),7.14 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.6 Hz, 1H), 6.27 (s, 1H), 4.76(d, J=4.5 Hz, 2H), 3.88 (s, 3H), 2.83 (s, 2H), 1.74 (t, J=4.5 Hz, 1H),1.35 (s, 6H).

EXAMPLE 70-EXAMPLE 70(1)

By the same procedure as described in example 45 using the compoundprepared in example 68(2) or example 68(3) in place of the compoundprepared in example 30(9), the following compounds of the presentinvention were given.

EXAMPLE 70(Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.54 (br, 1H),7.83 (d, J=8.2 Hz, 1H), 7.67 (dd, J=7.7, 1.7 Hz, 1H), 7.59 (dd, J=8.2,1.7 Hz, 1H), 7.50 (d, J=1.7 Hz, 1H), 7.39 (m, 1H), 7.05-6.96 (m, 2H),6.32 (s, 1H), 3.92 (s, 3H), 2.92 (s, 2H), 1.36 (s, 6H).

EXAMPLE 70(1)(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-cyanophenyl)ethan-1-one

TLC: Rf0.67 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.69 (br, 1H),7.83 (m, 1H), 7.77 (m, 1H), 7.63 (dt, J=1.3, 7.5 Hz, 1H), 7.54-7.47 (m,2H), 7.23-7.11 (m, 2H), 6.11 (s, 1H), 2.89 (s, 2H), 1.38 (s, 6H).

EXAMPLE 71(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-dimethylaminophenyl)ethan-1-one

By the same procedure as described in example 41 using the compoundprepared in example 62 in place of the compound prepared in example 38,the compound of the present invention having the following physical datawas given.

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.64 (br, 1H),7.90 (d, J=9.0 Hz, 2H), 7.35 (d, J=2.6 Hz, 1H), 7.11 (d, J=8.3 Hz, 1H),6.96 (dd, J=8.3, 2.6 Hz, 1H), 6.71 (d, J=9.0 Hz, 2H), 6.27 (s, 1H), 3.88(s, 3H), 3.04 (s, 6H), 2.81 (s, 2H), 1.33 (s, 6H).

EXAMPLE 72(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydroxyphenyl)ethan-1-one

To a solution of the compound prepared in example 60(9) (0.38 g) inbenzene (4 ml) was added butylamine (0.89 ml) and the mixture wasstirred for 4 hours at room temperature and overnight at 50° C. Themixture was cooled to room temperature and thereto was added a 1Naqueous solution of sodium hydroxide and the mixture was subjected toback extraction with ether. The extract was washed with water and brinesuccessively, dried over anhydrous magnesium sulfate and concentrated.The residue was washed with ether to give the compound of the presentinvention (0.25 g) having the following physical data.

TLC: Rf0.45 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.70 (br, 1H),7.87 (d, J=9.0 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H),6.98 (dd, J=8.2, 2.6 Hz, 1H), 6.87 (d, J=9.0 Hz, 2H), 6.23 (s, 1H), 5.96(br, 1H), 3.88 (s, 3H), 2.82 (s, 2H), 1.33 (s, 6H).

EXAMPLE 73(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((aminocarbonyl)amino)phenyl)ethan-1-one

Under atmosphere of argon, a solution of the compound prepared inexample 62 (150 mg) in tetrahydrofuran (2 ml) were added triethylamine(0.10 ml) and triphosgene (55 mg) at 0° C. for 30 minutes. To thereaction mixture was added ammonia water and the mixture was warmed toroom temperature and thereto was added water and was extracted withethyl acetate. The extract was washed with water and brine successively,dried over anhydrous magnesium sulfate and concentrated. The residue wasrecrystallized with a mixture of hexane and ethyl acetate to give thecompound of the present invention (103 mg) having the following physicaldata.

TLC: Rf0.57 (ethyl acetate); NMR (CDCl₃): δ 11.75 (br s, 1H), 7.90 (d,J=8.7 Hz, 2H), 7.38 (d, J=8.7 Hz, 2H), 7.33 (d, J=2.7 Hz, 1H), 7.13 (d,J=8.1 Hz, 1H), 6.99 (dd, J=8.1, 2.7 Hz, 1H), 6.90 (s, 1H), 6.24 (s, 1H),4.78 (s, 2H), 3.88 (s, 3H), 2.82 (s, 2H), 1.34 (s, 6H).

EXAMPLE 74-EXAMPLE 74(1)

By the same procedure as described in example 34 using the compoundprepared in example 66(1) or example 66 in place of the compoundprepared in example 33, the following compounds of the present inventionwere given.

EXAMPLE 74(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxycarbonylphenyl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.94 (br, 1H),8.10 (d, J=8.4 Hz, 2H), 7.98 (d, J=8.4 Hz, 2H), 7.34 (d, J=2.6 Hz, 1H),7.15 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.6 Hz, 1H), 6.27 (s, 1H), 3.94(s, 3H), 3.88 (s, 3H), 2.84 (s, 2), 1.36 (s, 6H).

EXAMPLE 74(1)(Z)-2-(7-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.61 (br, 1H),8.43 (d, J=1.8 Hz, 1H), 8.06 (dd, J=8.0, 1.7 Hz, 1H), 7.68 (dd, J=7.5,1.8 Hz, 1H), 7.38 (m, 1H), 7.28 (d, J=7.5 Hz, 1H), 7.05-6.96 (m, 2H),6.37 (s, 1H), 3.94 (s, 3H), 3.94 (s, 3H), 2.95 (s, 2H), 1.36 (s, 6H).

EXAMPLE 75(Z)-2-(7-(pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxyphenyl)ethan-1-one

By the same procedure as described in example 9 using the compoundprepared in example 60 in place of the compound prepared in example1(68) and 3-(diethylboryl)pyridine in place of benzeneboronic acid, thecompound of the present invention having the following physical data wasgiven.

TLC: Rf0.50 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.68 (br, 1H),8.86 (m, 1H), 8.62 (dd, J=5.0, 1.7 Hz, 1H), 7.93 (d, J=1.8 Hz, 1H), 7.89(d, J=8.0, 2.4, 1.7 Hz, 1H), 7.67 (dd, J=7.5, 1.8 Hz, 1H), 7.62 (dd,J=7.8, 1.8 Hz, 1H), 7.41-7.31 (m, 3H), 7.04-6.95 (m, 2H), 6.33 (s, 1H),3.91 (s, 3H), 2.95 (s, 2H), 1.40 (s, 6H).

EXAMPLE 76(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(1,3,4-oxadiazol-2-yl)phenyl)ethan-1-one

To a solution of the compound prepared in example 68(7) (0.20 g) inmethyl orthoformate (1.2 ml) was added p-toluenesulfonic acidmonohydrate (1 mg) and the mixture was refluxed for 30 minutes. Themixture was cooled to room temperature and thereto was added water, andextracted with ethyl acetate. The extract was washed with a saturatedaqueous solution of sodium bicarbonate, water and brine successively,dried over anhydrous magnesium sulfate and concentrated. The residue waswashed with a mixture of hexane and ethyl acetate (1/1) to give thecompound of the present invention (0.11 g) having the following physicaldata.

TLC: Rf0.56 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.95 (br, 1H),8.50 (s, 1H), 8.16 (d, J=8.4 Hz, 2H), 8.08 (d, J=8.4 Hz, 2H), 7.35 (d,J=2.5 Hz, 1H), 7.16 (d, J=8.2 Hz, 1H), 7.00 (dd, J=8.2, 2.5 Hz, 1H),6.29 (s, 1H), 3.89 (s, 3H), 2.86 (s, 2H), 1.38 (s, 6H).

EXAMPLE 77(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl)ethan-1-one

To a solution of the compound prepared in example 68 (0.35 g) inmethylene chloride (28 ml) were added methanesulfonyl chloride (96 μl)and methanesulfonic acid (0.27 ml) and the mixture was refluxedovernight. The reaction mixture was cooled to room temperature andthereto was added water and the mixture was extracted with methylenechloride. The aqueous layer was extracted with ethyl acetate. Thecombined organic layer was dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=2:1) to give the compound of thepresent invention (79.7 mg) having the following physical data.

TLC: Rf0.60 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.94 (br, 1H),8.01 (d, J=8.7 Hz, 2H), 7.96 (d, J=8.7 Hz, 2H), 7.35 (d, J=2.4 Hz, 1H),7.14 (d, J=8.1 Hz, 1H), 7.00 (d, J=8.1, 2.4 Hz, 1H), 6.28 (s, 1H), 4.13(s, 2H), 3.89 (s, 3H), 2.84 (s, 2H), 1.40 (s, 6H), 1.36 (s, 6H).

EXAMPLE 78(Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-hydroxyphenyl)ethan-1-one

By the same procedure as described in example 5 using the compoundprepared in example 11(42) in place of the compound prepared in example1(18), the compound of the present invention was given.

TLC: Rf0.50 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 11.28 (br, 1H),7.76 (dd, J=8.1, 1.8 Hz, 1H), 7.51 (dd, J=9.6, 2.4 Hz, 1H), 7.34 (m,1H), 7.23-7.12 (m, 2H), 6.94 (dd, J=8.4, 1.2 Hz, 1H), 6.85 (m, 1H), 6.25(s, 1H), 2.87 (s, 2H), 1.55 (s, 1H), 1.37 (s, 6H).

EXAMPLE 79(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-carboxyphenyl)ethan-1-one

To acetic acid (75 ml) was added the compound prepared in example 60(28)(4.29 g) was added concentrated hydrochloric acid (75 ml) and themixture was stirred for 1 day at 80° C. The reaction mixture was cooledwith ice, and it was added to sodium hydroxide (90 g) slowly to alkalifythe mixture. The aqueous layer was subjected to back extraction withether and acidified with a 2N hydrochloric acid and the mixture wasextracted. The extract was washed with water and brine successively,dried over anhydrous magnesium sulfate and concentrated to give thecompound of the present invention (2.79 g) having the following physicaldata.

TLC: Rf0.49 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.93 (br, 1H),8.65 (t, J=1.7 Hz, 1H), 8.22-8.16 (m, 2H), 7.56 (t, J=7.8 Hz, 1H), 7.37(d, J=2.6 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.6 Hz, 1H),6.30 (s, 1H), 3.90 (s, 3H), 2.85 (s, 2H), 2.20-1.20 (br, 1H), 1.37 (s,6H).

EXAMPLE 80-EXAMPLE 80(2)

By the same procedure as described in example 68 using the compoundprepared in example 60(29) or 79 in place of the compound prepared inexample 66(1), the compounds of the present invention were given.

EXAMPLE 80(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-carbamoylphenyl)ethan-1-one

TLC: Rf0.47 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.91 (br, 1H),8.34 (t, J=1.5 Hz, 1H), 8.09 (dt, J=7.7, 1.5 Hz, 1H), 7.98 (m, 1H), 7.54(t, J=7.7 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 7.01(dd, J=8.3, 2.5 Hz, 1H), 6.29 (s, 1H), 6.28 (br, 1H), 5.66 (br, 1H),3.89 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 80(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-(methylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.63 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.49 (br, 1H),7.73 (m, 1H), 7.54 (m, 1H), 7.48-7.40 (m, 2H), 7.22 (d, J=2.4 Hz, 1H),7.12 (d, J=8.2 Hz, 1H), 6.98 (dd, J=8.2, 2.4 Hz, 1H), 6.92 (m, 1H), 5.89(s, 1H), 3.84 (s, 3H), 2.92 (d, J=5.1 Hz, 3H), 2.84 (s, 2H), 1.36 (s,6H).

EXAMPLE 80(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(methylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.43 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.92 (br, 1H),8.27 (t, J=1.7 Hz, 1H), 8.06 (dt, J=7.7, 1.5 Hz, 1H), 7.93 (m, 1H), 7.51(t, J=7.7 Hz, 1H), 7.35 (d, J=2.6 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 7.00(dd, J=8.3, 2.6 Hz, 1H), 6.31 (br, 1H), 6.29 (s, 1H), 3.89 (s, 3H), 3.04(d, J=4.8 Hz, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 81(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(aminocarbonothioyl)phenyl)ethan-1-one

To a solution of the compound prepared in example 11(35) (0.3 g) inN,N-dimethylformamide (3 ml) were added magnesium chloride (0.13 g) andsodium hydrosulfide (0.11 g) under cooling with ice, and the mixture wasstirred for 3 hours at room temperature. To the reaction mixture wasadded water and the mixture was extracted with a mixture of ethylacetate and tetrahydrofuran. The extract was washed with water and brinesuccessively, dried over anhydrous magnesium sulfate and concentrated togive the compound of the present invention (0.33 g) having the followingphysical data. The given compound was used in the next reaction withoutsubjecting to purification.

TLC: Rf0.29 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.92 (br, 1H),8.02-7.54 (m, 4H), 7.67 (br, 1H), 7.34 (br, 1H), 7.33 (d, J=2.5 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.5 Hz, 1H), 6.25 (s, 1H), 3.88(s, 3H), 2.85 (s, 2H), 1.36 (s, 6H).

EXAMPLE 82(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-hydroxy-4-methyl-4,5-dihydro-1,3-thiazol-2-yl)phenyl)ethan-1-one

To a solution of the compound prepared in example 81 (0.33 g) in ethanol(18 ml) were added sodium bicarbonate (0.13 g) and bromoacetone (0.11 g)and the mixture was stirred overnight at 70° C. The reaction mixture wascooled to room temperature, and thereto was added water and the mixturewas extracted with ethyl acetate. The extract was washed with water andbrine successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=1:1) to give the compound of thepresent invention (0.30 g) having the following physical data.

TLC: Rf0.48 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.94 (br, 1H),7.98 (d, J=8.3 Hz, 2H), 7.92 (d, J=8.3 Hz, 2H), 7.34 (d, J=2.5 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.00 (dd, J=8.3, 2.5 Hz, 1H), 6.28 (s, 1H), 3.89(s, 3H), 3.52 (d, J=11.9 Hz, 1H), 3.44 (dd, J=11.9 Hz, 1H), 2.96 (s,1H), 2.84 (s, 2H), 1.75 (s, 3H), 1.36 (s, 6H).

EXAMPLE 83(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methyl-1,3-thiazol-2-yl)phenyl)ethan-1-one

To a solution of the compound prepared in example 82 (0.29 g) in dioxane(3.5 ml) was added a 4N solution of hydrogen chloride in dioxane (1.7ml) and the mixture was stirred for 2 hours at room temperature. Thereaction mixture was neutralized with a 1N aqueous solution of sodiumhydroxide and the mixture was extracted with ethyl acetate. The extractwas washed with water and brine successively, dried over anhydrousmagnesium sulfate, and concentrated to give the compound of the presentinvention (0.20 g) having the following physical data.

TLC: Rf0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.92 (br, 1H),8.00 (s, 4H), 7.36 (d, J=2.5 Hz, 1H), 7.15 (d, J=8.2 Hz, 1H), 7.00 (dd,J=8.2, 2.5 Hz, 1H), 6.92 (m, 1H), 6.30 (s, 1H), 3.89 (s, 3H), 2.84 (s,2H), 2.53 (d, J=0.9 Hz, 3H), 1.36 (s, 6H).

EXAMPLE 84-EXAMPLE 84(444)

The compounds of example 84-example 84(444) were prepared according tothe following method.

The Method for the Preparation of Example 84-84(306) (Amide Compound)

To a solution of an aniline compound (30 μmol) in pyridine (60 μl) wasadded a solution of acid chloride 1 (30 μmol) in methylene chloride (60μl), and the mixture was stirred overnight at room temperature. To thereaction mixture was added phthalic anhydride (15 μmol) intetrahydrofuran (15 μl) and 2 hours later to the mixture was addedPS-trisamine (ca. 50 mg, tris-(2-aminoethyl)amine polystylene (resin)).1 hour later thereto was added methylene chloride (1 ml) and the resinwas filtered and was washed with methylene chloride (1 ml). The filtratewas concentrated to give an amide compound.

The method for the preparation of example 84(307)-84(417) (sulfonamidecompound) or example 84(418)-84(444) (carbamate compound)

To a solution of an aniline compound (30 μmol) in pyridine (60 μl) wereadded a solution of acid chloride 2 or acid chloride 3 (60 μmol) inmethylene chloride (60 μl), and the mixture was stirred overnight atroom temperature. To the reaction mixture was added phthalic anhydride(15 μmol) in tetrahydrofuran (15 μl) and 2 hours later was addedPS-trisamine (ca. 50 mg). 1 hour later thereto was added methylenechloride (1 ml) and the resin was filtered and was washed with methylenechloride (1 ml). The filtrate was concentrated to give a sulfonamide orcarbamate compound.

The condition under which HPLC was measured is as follows.

-   Column:XTerra C18, 4.6×50 mm (5 em),-   Rate of flow: 3 ml/min,-   Solvent-   Solvent A: a 0.1% aqueous solution of trifluoroacetic acid,-   Solvent B: a 0.1% solution of trifluoroacetic acid in acetonitrile    Ratio of Solvent:

At first, the ratio of solvent A/solvent B was fixed to 95/5 for first0.5 minute. Next the ratio was changed to 0/100 linearly in 2.5 minutesand the ratio was fixed to 0/100 for 0.5 minute. Afterwards, the ratiowas changed to 95/5 in 0.01 minute and the ratio was fixed to 95/5 for1.49 minutes.

EXAMPLE 84(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((naphthalen-1-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(pivaloylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(3)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(hexanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclohexylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(benzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((furan-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 417 (M+H)⁺.

EXAMPLE 84(7)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(acetylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.71; Mass (ESI, Pos. 20V): m/z 365 (M+H)⁺.

EXAMPLE 84(8)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclopropylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 84(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-phenylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.36; Mass (ESI, Pos. 20V): m/z 503 (M+H)⁺.

EXAMPLE 84(10)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(11)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(12)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,6-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(13)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(14)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,5-ditrifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.46; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(15)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-hexylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.68; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(16)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chloro-5-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(17)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(18)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-butylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.48; Mass (ESI, Pos. 20V): m/z 483 (M+H)⁺.

EXAMPLE 84(19)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4,6-trichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.30; Mass (ESI, Pos. 20V): m/z 529 (M+H)⁺,531 (M+2+H)⁺.

EXAMPLE 84(20)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chlorobenzothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.51; Mass (ESI, Pos. 20V): m/z 517 (M+H)⁺.

EXAMPLE 84(21)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chloro-4-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(22)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,5-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.45; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(23)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,4-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(24)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-hexyloxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.60; Mass (ESI, Pos. 20V): m/z 527 (M+H)⁺.

EXAMPLE 84(25)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,4-dimethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(26)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-butoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.39; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(27)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,3-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(28)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(29)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,5-dimethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(30)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-3-(2-chloro-6-fluorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 560 (M+H)⁺.

EXAMPLE 84(31)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-3-(2-chlorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 542 (M+H)⁺.

EXAMPLE 84(32)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-3-(2,6-dichlorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 576 (M+H)⁺.

EXAMPLE 84(33)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(34)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(5-fluoro-2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(35)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-hexyloxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.49; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(36)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,5-ditrifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(37)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4-dichloro-5-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(38)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-pentylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.57; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺.

EXAMPLE 84(39)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(40)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(41)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(42)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclopentylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 419 (M+H)⁺.

EXAMPLE 84(43)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(44)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(45)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-ethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(46)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-propylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.36; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(47)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,6-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(48)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(49)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-methoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(50)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.47; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 84(51)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.46; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 84(52)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-phenylpropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(53)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenoxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(54)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 536 (M+H)⁺.

EXAMPLE 84(55)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-methylphenyl)thiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 550 (M+H)⁺.

EXAMPLE 84(56)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 84(57)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-methoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(58)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(thiophen-2-yl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(59)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-chloropentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(60)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(61)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(isobutyrylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.95; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 84(62)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-cyclopentylpropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(63)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(octanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.42; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(64)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(nonanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.52; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(65)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 84(66)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(67)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chloropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 413 (M+H)⁺.

EXAMPLE 84(68)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-chlorobutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(69)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-butenoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 84(70)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methyl-2-butenoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 84(71)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(72)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3,3-dimethylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(73)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(74)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((thiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(75)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(1,4-benzodioxan-2-yl)thiazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 568 (M+H)⁺.

EXAMPLE 84(76)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 84(77)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-methylcyclohexylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.30; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(78)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,6,6-trimethyl-1-cyclohexen-1-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.35; Mass (ESI, Pos. 20V): m/z 473 (M+H)⁺.

EXAMPLE 84(79)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(80)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(81)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(5-fluoro-2-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 459 (M+H)⁺.

EXAMPLE 84(82)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethoxy-2-oxoacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(83)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-3-phenylisoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(84)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chlorothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 84(85)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-chlorophenylthio)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 570 (M+H)⁺.

EXAMPLE 84(86)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5,6-dichloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 496 (M+H)⁺.

EXAMPLE 84(87)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-2-phenyl-2H-1,2,3-triazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.53; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(88)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,6-dimethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(89)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,5-dichlorothiophen-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 501 (M+H)⁺.

EXAMPLE 84(90)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-propylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(91)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((6-chloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 84(92)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((naphthalen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(93)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-benzyloxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(94)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclobutylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 84(95)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(96)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,3,4-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(97)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((benzothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 483 (M+H)⁺.

EXAMPLE 84(98)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chloro-2,2,3,3-tetrafluoropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(99)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,2,3,3-tetrafluoropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 451 (M+H)⁺.

EXAMPLE 84(100)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-methoxyphenyl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(101)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,2,2-trichloroacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺,469 (M+2+H)⁺.

EXAMPLE 84(102)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-chloropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V): m/z 413 (M+H)⁺.

EXAMPLE 84(103)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(104)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-cyanobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 452 (M+H)⁺.

EXAMPLE 84(105)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-chlorophenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.41; Mass (ESI, Pos. 20V): m/z 554 (M+H)⁺.

EXAMPLE 84(106)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-methylphenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.40; Mass (ESI, Pos. 20V): m/z 534 (M+H)⁺.

EXAMPLE 84(107)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-(4-chlorophenyl)-5-propylisoimidazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.46; Mass (ESI, Pos. 20V): m/z 569 (M+H)⁺.

EXAMPLE 84(108)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-propylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 502 (M+H)⁺.

EXAMPLE 84(109)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-chloro-3-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(110)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-nitro-4-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 486 (M+H)⁺.

EXAMPLE 84(111)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydra-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-chlorophenoxy)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 491 (M+H)⁺.

EXAMPLE 84(112)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-ethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(113)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-ethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(114)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(115)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-methylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(116)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 84(117)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methylthiopropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 425 (M+H)⁺.

EXAMPLE 84(118)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.78; Mass (ESI, Pos. 20V): m/z 519 (M+H)⁺.

EXAMPLE 84(119)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-cyclopentylacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(120)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 474 (M+H)⁺.

EXAMPLE 84(121)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenoxybutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(122)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-chlorophenyl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 84(123)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(124)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-nitro-4-methylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 480 (M+H)⁺.

EXAMPLE 84(125)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(pentanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(126)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(127)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,5-dimethylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 445(M+H)⁺.

EXAMPLE 84(128)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,3,6-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(129)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(130)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chloro-4-mesylthiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 545 (M+H)⁺.

EXAMPLE 84(131)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3,5-dimethylthioisoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.32; Mass (ESI, Pos. 20V): m/z 526 (M+H)⁺.

EXAMPLE 84(132)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(133)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-isopropylsulfonyl-3-chlorothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 573 (M+H)⁺.

EXAMPLE 84(134)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-(4-chlorophenyl)-2-methylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.64; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(135)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,5-dichloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 496 (M+H)⁺.

EXAMPLE 84(136)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-benzyl-3-t-butylisoimidazol-5-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.57; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(137)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-t-butyl-1-methylisoimidazol-5-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(138)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-chlorobutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(139)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-fluoro-2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(140)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(butanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 84(141)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5,5-dimethyl-3-methylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.43; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(142)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(propanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 84(143)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methyl-2-trifluoromethylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(144)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-t-butyl-2-methylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.51; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(145)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,4,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(146)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(147)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,3,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(148)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,3-dimethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(149)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chloro-6-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 479 (M+H)⁺.

EXAMPLE 84(150)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-chloro-6-methylpyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 476 (M+H)⁺.

EXAMPLE 84(151)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-(4-trifluoromethoxyphenyl)-2-propenoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.39; Mass (ESI, Pos. 20V): m/z 537 (M+H)⁺.

EXAMPLE 84(152)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methoxycarbonylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(153)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-ethoxycarbonylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.97; Mass (ESI, Pos. 20V): m/z 465 (M+H)⁺.

EXAMPLE 84(154)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((naphthalen-1-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(155)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(pivaloylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(156)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(157)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(hexanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(158)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclohexylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(159)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(benzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(160)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((furan-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 417 (M+H)⁺.

EXAMPLE 84(161)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(acetylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.67; Mass (ESI, Pos. 20V): m/z 365 (M+H)⁺.

EXAMPLE 84(162)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclopropylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.84; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 84(163)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-phenylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 503 (M+H)⁺.

EXAMPLE 84(164)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(165)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.24; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(166)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,6-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(167)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(168)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,5-ditrifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.44; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(169)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-hexylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.65; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(170)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chloro-5-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(171)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(172)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-butylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.43; Mass (ESI, Pos. 20V): m/z 483 (M+H)⁺.

EXAMPLE 84(173)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chlorobenzothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.48; Mass (ESI, Pos. 20V): m/z 517 (M+H)⁺.

EXAMPLE 84(174)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chloro-4-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(175)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,5-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.42; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(176)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,4-dichlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 495 (M+H)⁺.

EXAMPLE 84(177)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-hexyloxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.56; Mass (ESI, Pos. 20V): m/z 527 (M+H)⁺.

EXAMPLE 84(178)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,4-dimethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(179)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-butoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(180)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,3-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(181)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(182)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,5-dimethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(183)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-3-(2-chloro-6-fluorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 560 (M+H)⁺.

EXAMPLE 84(184)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-3-(2-chlorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 542 (M+H)⁺.

EXAMPLE 84(185)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-3-(2,6-dichlorophenyl)isoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 576 (M+H)⁺.

EXAMPLE 84(186)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(187)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(5-fluoro-2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(188)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-pentyloxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.46; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(189)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,5-ditrifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(190)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4-dichloro-5-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(191)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-pentylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.53; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺.

EXAMPLE 84(192)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(193)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(194)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(195)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclopentylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 419 (M+H)⁺.

EXAMPLE 84(196)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(197)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(198)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-ethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(199)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-propylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(200)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,6-difluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(201)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(202)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-methoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(203)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.46; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 84(204)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.43; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 84(205)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-phenylpropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(206)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenoxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(207)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 536 (M+H)⁺.

EXAMPLE 84(208)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-methylphenyl)thiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 550 (M+H)⁺.

EXAMPLE 84(209)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 84(210)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-methoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(211)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(thiophen-2-yl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(212)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-chloropentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(213)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(214)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(isobutyrylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 84(215)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-cyclopentylpropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(216)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(octanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(217)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(nonanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.48; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(218)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 84(219)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 84(220)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chloropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.88; Mass (ESI, Pos. 20V): m/z 413 (M+H)⁺.

EXAMPLE 84(221)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-chlorobutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.97; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(222)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-butenoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.87; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 84(223)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methyl-2-butenoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 84(224)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(225)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3,3-dimethylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(226)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(227)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((thiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(228)-benzodioxan-2-yl)thiazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.35; Mass (ESI, Pos. 20V): m/z 568 (M+H)⁺.

EXAMPLE 84(229)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-chlorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 461 (M+1H)⁺.

EXAMPLE 84(230)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-methylcyclohexylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 84(231)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,6,6-trimethyl-1-cyclohexen-1-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 473 (M+H)⁺.

EXAMPLE 84(232)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-trifluoromethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(233)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4-ditrifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(234)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(5-fluoro-2-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 459 (M+H)⁺.

EXAMPLE 84(235)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethoxy-2-oxoacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(236)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-3-phenylisoxazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(237)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chlorothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 84(238)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-chlorophenylthio)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 570 (M+H)⁺.

EXAMPLE 84(239)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5,6-dichloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 496 (M+H)⁺.

EXAMPLE 84(240)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-2-phenyl-2H-1,2,3-triazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.48; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(241)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,6-dimethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(242)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,5-dichlorothiophen-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 501 (M+H)⁺.

EXAMPLE 84(243)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-propylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 84(244)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((6-chloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 84(245)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((naphthalen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(246)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-benzyloxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(247)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclobutylcarbonylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 84(248)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(249)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,3,4-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(250)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((benzothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 483 (M+H)⁺.

EXAMPLE 84(251)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chloro-2,2,3,3-tetrafluoropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(252)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,2,3,3-tetrafluoropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 451 (M+H)⁺.

EXAMPLE 84(253)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-methoxyphenyl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(254)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,2,2-trichloroacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺,469 (M+2+H)⁺.

EXAMPLE 84(255)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-chloropropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.97; Mass (ESI, Pos. 20V): m/z 413 (M+H)⁺.

EXAMPLE 84(256)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 472 (M+H)⁺.

EXAMPLE 84(257)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-cyanobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 452 (M+H)⁺.

EXAMPLE 84(258)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-chlorophenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.38; Mass (ESI, Pos. 20V): m/z 554 (M+H)⁺.

EXAMPLE 84(259)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-methylphenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 534 (M+H)⁺.

EXAMPLE 84(260)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-(4-chlorophenyl)-5-propylisoimidazol-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.43; Mass (ESI, Pos. 20V): m/z 569 (M+H)⁺.

EXAMPLE 84(261)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-propylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 502 (M+H)⁺.

EXAMPLE 84(262)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-chloro-3-nitrobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 84(263)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-nitro-4-methylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 486 (M+H)⁺.

EXAMPLE 84(264)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-chlorophenoxy)pyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 491 (M+H)⁺.

EXAMPLE 84(265)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-ethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(266)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-ethoxybenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.30; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 84(267)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(268)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-methylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(269)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methoxyacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.76; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 84(270)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methylthiopropanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.88; Mass (ESI, Pos. 20V): m/z 425 (M+H)⁺.

EXAMPLE 84(271)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.75; Mass (ESI, Pos. 20V): m/z 519 (M+H)⁺.

EXAMPLE 84(272)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-cyclopentylacetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 84(273)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 474 (M+H)⁺.

EXAMPLE 84(274)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenoxybutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.23; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(275)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(4-chlorophenyl)acetyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 84(276)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methylpentanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(277)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-nitro-4-methylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 480 (M+H)⁺.

EXAMPLE 84(278)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(pentanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(279)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methylbutanoyl)amino)phenyl)ethan-1′-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V) m/z 407 (M+H)⁺.

EXAMPLE 84(280)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,5-dimethylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 84(281)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,3,6-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(282)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(283)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chloro-4-mesylthiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V): m/z 545 (M+H)⁺.

EXAMPLE 84(284)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3,5-dimethylthioisoxazol0-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 526 (M+H)⁺.

EXAMPLE 84(285)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethylthiopyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(286)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-isopropylsulfonyl-3-chlorothiophen-2-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 573 (M+H)⁺.

EXAMPLE 84(287)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-(4-chlorophenyl)-2-methylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.60; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(288)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,5-dichloropyridin-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 496 (M+H)⁺.

EXAMPLE 84(289)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-benzyl-3-t-butylisoimidazolisoimidazol-5-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.56; Mass (ESI, Pos. 20V): m/z 563 (M+H)⁺.

EXAMPLE 84(290)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-t-butyl-1-methylisoimidazol-5-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(291)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-chlorobutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 84(292)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-fluoro-2-trifluoromethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(293)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(butanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 84(294)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5,5-dimethyl-3-methylhexanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.39; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(295)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(propanoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 84(296)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methyl-2-trifluoromethylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(297)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-t-butyl-2-methylfuran-3-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.47; Mass (ESI, Pos. 20V): m/z 487 (M+H)⁺.

EXAMPLE 84(298)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,4,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.24; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(299)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(300)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,3,5-trifluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(301)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,3-dimethylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 84(302)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chloro-6-fluorobenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 479 (M+H)⁺.

EXAMPLE 84(303)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-chloro-6-methylpyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 476 (M+H)⁺.

EXAMPLE 84(304)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-(4-trifluoromethoxyphenyl)-2-propenoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.35; Mass (ESI, Pos. 20V): m/z 537 (M+H)⁺.

EXAMPLE 84(305)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methoxycarbonylbenzoylamino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 485 (M+H)⁺.

EXAMPLE 84(306)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-ethoxycarbonylbutanoyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 465 (M+H)⁺.

EXAMPLE 84(307)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(mesylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.79; Mass (ESI, Pos. 20V): m/z 401 (M+H)⁺.

EXAMPLE 84(308)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pentylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(309)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((isopropylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 429 (M+H)⁺.

EXAMPLE 84(310)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-chlorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺.

EXAMPLE 84(311)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-iodophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 589 (M+H)⁺.

EXAMPLE 84(312)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-nitrophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(313)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-mesylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(314)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(315)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-phenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(316)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.30; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(317)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,6-difluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(318)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,5-difluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(319)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,5-dimethoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 523 (M+H)⁺.

EXAMPLE 84(320)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((naphthalen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(321)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(naphthalen-1-yl)ethylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(322)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylethenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 489 (M+H)⁺.

EXAMPLE 84(323)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((furan-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 453 (M+H)⁺.

EXAMPLE 84(324)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((thiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(325)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-bromo-2,5-dichlorothiophen-3-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.40; Mass (ESI, Pos. 20V): m/z 617 (M+H)⁺.

EXAMPLE 84(326)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-phenylsulfonylthiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 609 (M+H)⁺.

EXAMPLE 84(327)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(7-chloro-2,1,3-benzoxadiazol-4-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(328)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-acetylamino-4-methylthioazol-5-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.82; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(329)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-methoxydibenzo[b,d]furan-3-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 583 (M+H)⁺.

EXAMPLE 84(330)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3,4-dichlorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(331)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 493 (M+H)⁺.

EXAMPLE 84(332)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(benzylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(333)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(phenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(334)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4:1; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(335)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(336)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-fluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(337)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(338)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(339)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-ethenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 489 (M+H)⁺.

EXAMPLE 84(340)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(quinolin-8-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 514 (M+H)⁺.

EXAMPLE 84(341)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-acetylaminophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 520 (M+H)⁺.

EXAMPLE 84(342)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chloro-4-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 522 (M+H)⁺.

EXAMPLE 84(343)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 493 (M+H)⁺.

EXAMPLE 84(344)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-nitro-4-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 538 (M+H)⁺.

EXAMPLE 84(345)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-methoxy-5-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 507 (M+H)⁺.

EXAMPLE 84(346)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,4,6-trimethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(347)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-butoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.36; Mass (ESI, Pos. 20V): m/z 535 (M+H)⁺.

EXAMPLE 84(348)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-fluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(349)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(350)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-chloro-4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(351)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-chloro-6-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(352)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-nitro-4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 522 (M+H)⁺.

EXAMPLE 84(353)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(354)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(355)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(5-bromo-2-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 571 (M+H)⁺,573 (M+2+H)⁺.

EXAMPLE 84(356)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-nitro-4-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 576 (M+H)⁺.

EXAMPLE 84(357)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-bromo-2-trifluoromethoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.38; Mass (ESI, Pos. 20V): m/z 625 (M+H)⁺,627 (M+2+H)⁺.

EXAMPLE 84(358)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-isopropylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(359)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(naphthalen-1-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(360)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-t-butylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 519 (M+H)⁺.

EXAMPLE 84(361)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-(3-(5-dimethylaminonaphthalen-1-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.95; Mass (ESI, Pos. 20V): m/z 556 (M+H)⁺.

EXAMPLE 84(362)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(5-((phenylcarbonyl)aminomethyl)thiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 602 (M+H)⁺.

EXAMPLE 84(363)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(mesylamino)phenyl)ethan-1-one

HPLC retention time (min.): 3.75; Mass (ESI, Pos. 20V): m/z 401 (M+H)⁺.

EXAMPLE 84(364)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pentylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(365)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((isopropylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 429 (M+H)⁺.

EXAMPLE 84(366)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-chlorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺.

EXAMPLE 84(367)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-iodophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 589 (M+H)⁺.

EXAMPLE 84(368)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-nitrophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 508 (M+H)⁺.

EXAMPLE 84(369)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-mesylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(370)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.21; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(371)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-phenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(372)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(373)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,6-difluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(374)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,5-difluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 499 (M+H)⁺.

EXAMPLE 84(375)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,5-dimethoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 523 (M+H)⁺.

EXAMPLE 84(376)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((naphthalen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(377)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(naphthalen-1-yl)ethylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(378)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylethenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 489 (M+H)⁺.

EXAMPLE 84(379)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((furan-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 453 (M+H)⁺.

EXAMPLE 84(380)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((thiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 84(381)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-bromo-2,5-dichlorothiophen-3-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.36; Mass (ESI, Pos. 20V): m/z 617 (M+H)⁺.

EXAMPLE 84(382)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-phenylsulfonylthiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 609 (M+H)⁺.

EXAMPLE 84(383)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(7-chloro-2,1,3-benzoxadiazol-4-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 539 (M+H)⁺.

EXAMPLE 84(384)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-acetylamino-4-methylthiazol-5-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 541 (M+H)⁺.

EXAMPLE 84(385)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-methoxydibenzo[b,d]furan-3-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.29; Mass (ESI, Pos. 20V): m/z 583 (M+H)⁺.

EXAMPLE 84(386)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3,4-dichlorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(387)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 493 (M+H)⁺.

EXAMPLE 84(388)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(benzylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(389)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(phenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 463 (M+H)⁺.

EXAMPLE 84(390)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(391)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(392)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-fluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(393)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(394)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 488 (M+H)⁺.

EXAMPLE 84(395)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-ethenylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.14; Mass (ESI, Pos. 20V): m/z 489 (M+H)⁺.

EXAMPLE 84(396)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(quinolin-8-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 514 (M+H)⁺.

EXAMPLE 84(397)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-acetylaminophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.79; Mass (ESI, Pos. 20V): m/z 520 (M+H)⁺.

EXAMPLE 84(398)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chloro-4-cyanophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 522 (M+H)⁺.

EXAMPLE 84(399)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 493 (M+H)⁺.

EXAMPLE 84(400)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-nitro-4-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 538 (M+H)⁺.

EXAMPLE 84(401)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-methoxy-5-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 507 (M+H)⁺.

EXAMPLE 84(402)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,4,6-trimethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(403)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-butoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.33; Mass (ESI, Pos. 20V): m/z 535 (M+H)⁺.

EXAMPLE 84(404)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-fluorophenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 481 (M+H)⁺.

EXAMPLE 84(405)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 477 (M+H)⁺.

EXAMPLE 84(406)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-chloro-4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.24; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(407)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-chloro-6-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 511 (M+H)⁺.

EXAMPLE 84(408)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-nitro-4-methylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 522 (M+H)⁺.

EXAMPLE 84(409)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(410)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-trifluoromethylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 531 (M+H)⁺.

EXAMPLE 84(411)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(5-bromo-2-methoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 571 (M+H)⁺,573 (M+2+H)⁺.

EXAMPLE 84(412)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-bromo-2-trifluoromethoxyphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 625 (M+1H)⁺,627 (M+2+H)⁺.

EXAMPLE 84(413)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-isopropylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(414)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(naphthalen-1-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 513 (M+H)⁺.

EXAMPLE 84(415)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-t-butylphenylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.31; Mass (ESI, Pos. 20V): m/z 519 (M+H)⁺.

EXAMPLE 84(416)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(5-dimethylaminonaphthalen-1-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 556 (M+H)⁺.

EXAMPLE 84(417)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(5-((phenylcarbonyl)aminomethyl)thiophen-2-ylsulfonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 602 (M+H)⁺.

EXAMPLE 84(418)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((isobutyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.24; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(419)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethylhexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.66; Mass (ESI, Pos. 20V): m/z 479 (M+H)⁺.

EXAMPLE 84(420)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((ethoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 84(421)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-propenyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(422)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3′-((propoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.15; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 84(423)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((butoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.26; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(424)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((hexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.48; Mass (ESI, Pos. 20V): m/z 451 (M+H)⁺.

EXAMPLE 84(425)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,2,2,-trichloroethoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.32; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺,499 (M+2+H)⁺.

EXAMPLE 84(426)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.74; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(427)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((isopropyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 84(428)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-butenyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(429)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.73; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(430)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((t-butoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(431)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((benzyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 84(432)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((isobutyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(433)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethylhexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.59; Mass (ESI, Pos. 20V): m/z 479 (M+H)⁺.

EXAMPLE 84(434)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((ethoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 3.96; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 84(435)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-propenyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 84(436)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((propoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 84(437)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((butoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.19; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 84(438)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((hexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.43; Mass (ESI, Pos. 20V): m/z 451 (M+H)⁺.

EXAMPLE 84(439)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,2,2,-trichloroethoxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.28; Mass (ESI, Pos. 20V): m/z 497 (M+H)⁺.

EXAMPLE 84(440)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.68; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(441)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((isopropyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 84(442)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-oxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 84(443)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.69; Mass (ESI, Pos. 20V): m/z 505 (M+H)⁺.

EXAMPLE 84(444)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((benzyloxycarbonyl)amino)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 85(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-hydroxycarbamoylphenyl)ethan-1-one

To a solution of the compound prepared in example 66(1) (0.15 g) intetrahydrofuran (2 ml) were added triethylamine (89 μl) andchloroethylformate (61 μl) and the mixture was stirred for 1 hour at 0°C. To the reaction mixture was added a 50% aqueous solution ofhydroxylamine (0.1 ml) and the mixture was stirred for 1 hour at roomtemperature. To the reaction mixture was added water and the mixture wasextracted with ethyl acetate. The extract was washed with a saturatedaqueous solution of sodium bicarbonate, water and brine successively,dried over anhydrous magnesium sulfate and concentrated. The residue waswashed with a mixture of hexane and ethyl acetate to give the compoundof the present invention (69.8 mg) having the following physical data.

TLC: Rf0.35 (chloroform:methanol=10:1); NMR (DMSO-d₆): δ 11.98 (s, 1H),11.30 (br, 1H), 9.11 (br, 1H), 8.07 (d, J=8.1 Hz, 2H), 7.80 (d, J=8.1Hz, 2H), 7.57 (d, J=2.6 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 7.10 (dd,J=8.4, 2.6 Hz, 1H), 6.47 (s, 1H), 3.85 (s, 3H), 2.85 (s, 2H), 1.28 (s,6H).

EXAMPLE 86-EXAMPLE 86(27)

By the same procedure as described in example 56 using the compoundprepared in reference example 17 or a corresponding derivative and4-nitrophenacyl bromide or a corresponding derivative, the followingcompounds of the present invention were given.

EXAMPLE 86(Z)-2-(6-difluoromethoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.29 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.54 (br, s,1H), 8.06 (d, J=9.0 Hz, 2H), 7.75 (d, J=9.0 Hz, 2H), 7.50 (d, J=1.5 Hz,1H), 7.43 (d, J=8.4 Hz, 1H), 7.34 (dd, J=8.4, 1.5 Hz, 1H), 6.58 (t,J=73.5 Hz, 1H), 6.29 (s, 1H), 1.61 (s, 6H).

EXAMPLE 86(1)(Z)-2-(6-difluoromethoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.31 (br, s,1H), 7.99 (d, J=9.0 Hz, 2H), 7.48 (d, J=1.8 Hz, 1H), 7.39 (d, J=8.1 Hz,1H), 7.29 (dd, J=8.1, 1.8 Hz, 1H), 6.96 (d, J=9.0 Hz, 2H), 6.57 (t,J=73.5 Hz, 1H), 6.30 (s, 1H), 3.88 (s, 3H), 1.58 (s, 6H).

EXAMPLE 86(2)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.20 (br, s,1H), 8.01 (d, J=9.0 Hz, 2H), 7.22 (d, J=2.4 Hz, 1H), 7.20 (d, J=8.4 Hz,1H), 7.07 (dd, J=8.4, 2.4 Hz, 1H), 6.96 (d, J=9.0 Hz, 2H), 6.30 (s, 1H),3.91 (s, 3H), 3.87 (s, 3H), 2.05-1.80 (m, 4H), 0.65 (t, J=7.5 Hz, 6H).

EXAMPLE 86(3)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.42 (br, s,1H), 8.08 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.24 (d, J=8.4 Hz,1H), 7.22 (d, J=1.8 Hz, 1H), 7.11 (dd, J=8.4, 1.8 Hz, 1H), 6.29 (s, 1H),3.91 (s, 3H), 2.10-1.80 (m, 4H), 0.65 (t, J=7.5 Hz, 6H).

EXAMPLE 86(4)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.57 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.46 (br, s,1H), 8.30 (d, J=9.0 Hz, 2H), 8.14 (d, J=9.0 Hz, 2H), 7.30-7.20 (m, 2H),7.12 (dd, J=7.8, 1.8 Hz, 1H), 6.32 (s, 1H), 3.92 (s, 3H), 2.10-1.85 (m,4H), 0.66 (t, J=7.5 Hz, 6H).

EXAMPLE 86(5)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-nitrophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.50-10.35 (br,1H), 8.83 (t, J=2.1 Hz, 1H), 8.40-8.25 (m, 2H), 7.64 (t, J=7.8 Hz, 1H),7.30-7.20 (m, 2H), 7.13 (dd, J=8.4, 2.4 Hz, 1H), 6.34 (s, 1H), 3.94 (s,3H), 2.10-1.85 (m, 4H), 0.66 (t, J=7.5 Hz, 6H).

EXAMPLE 86(6)(Z)-2-(6-methoxy-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzothiazin-4-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.49 (s, 1H),7.99 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.33 (d, J=2.7 Hz, 1H),7.30 (d, J=8.4 Hz, 1H), 7.03 (dd, J=8.4, 2.7 Hz, 1H), 6.15 (s, 1H), 3.89(s, 3H), 1.74 (s, 6H).

EXAMPLE 86(7)(Z)-2-(6-methoxy-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzothiazin-4-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.28 (s, 1H),7.92 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.7 Hz, 1H), 7.27 (d, J=8.7 Hz, 1H),6.99 (dd, J=8.7, 2.7 Hz, 1H), 6.94 (d, J=8.7 Hz, 2H), 6.18 (s, 1H), 3.89(s, 3H), 3.87 (s, 3H), 1.71 (s, 6H).

EXAMPLE 86(8)(Z)-2-(6-methoxy-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzothiazin-4-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 1.75 (s, 6H) 3.90(s, 3H) 6.18 (s, 1H) 7.03 (dd, J=8.55, 2.75 Hz, 1H) 7.30 (d, J=8.55 Hz,1H) 7.34 (d, J=2.75 Hz, 1H) 8.05 (d, J=8.85 Hz, 2H) 8.29 (d, J=8.55 Hz,2H) 12.54 (s, 1H).

EXAMPLE 86(9)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.14 (br, 1H),8.28 (d, J=9.0 Hz, 2H), 8.07 (d, J=9.0 Hz, 2H), 7.32 (d, J=2.4 Hz, 1H),7.16 (d, J=8.6 Hz, 1H), 7.01 (dd, J=8.6, 2.4 Hz, 1H), 6.26 (s, 1H), 3.88(s, 3H), 2.85 (s, 2H), 1.73-1.57 (m, 4H), 0.95 (t, J=7.5 Hz, 6H).

EXAMPLE 86(10)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-dimethylamino-3-bromopyridin-5-yl)ethan-1-one

TLC: Rf0.56 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.69 (br, 1H),8.74 (d, J=2.0 Hz, 1H), 8.32 (d, J=2.0 Hz, 1H), 7.29 (d, J=2.8 Hz, 1H),7.13 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.8 Hz, 1H), 6.13 (s, 1H), 3.88(s, 3H), 3.11 (s, 6H), 2.83 (s, 2H), 1.34 (s, 6H).

EXAMPLE 86(11)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-dimethylaminopyridin-5-yl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.59 (br, 1H),8.83 (d, J=2.4 Hz, 1H), 8.07 (dd, J=8.8, 2.4 Hz, 1H), 7.30 (d, J=2.8 Hz,1H), 7.11 (d, J=8.3 Hz, 1H), 6.97 (dd, J=8.3, 2.8 Hz, 1H), 6.54 (d,J=8.8 Hz, 1H), 6.21 (s, 1H), 3.87 (s, 3H), 3.17 (s, 6H), 2.81 (s, 2H),1.33 (s, 6H).

EXAMPLE 86(12)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-nitrophenyl)ethan-1-one

TLC: Rf0.47 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 10.57 (s, 1H),8.82 (t, J=1.8 Hz, 1H), 8.36-8.30 (m, 2H), 7.64 (t, J=8.1 Hz, 1H), 7.33(d, J=8.4 Hz, 1H), 7.26 (m, 1H), 7.13 (dd, J=8.4, 2.4 Hz, 1H), 6.33 (s,1H), 3.94 (s, 3H), 1.60 (s, 6H).

EXAMPLE 86(13)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-nitrophenyl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 12.10 (br, 1H),8.77 (t, J=2.0 Hz, 1H), 8.31-8.26 (m, 2H), 7.61 (t, J=8.0 Hz, 1H), 7.34(d, J=2.5 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.5 Hz, 1H),6.27 (s, 1H), 3.89 (s, 3H), 2.86 (s, 2H), 1.75-1.55 (m, 4H), 0.96 (t,J=7.5 Hz, 6H).

EXAMPLE 86(14)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-methoxypyridin-5-yl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 11.71 (br, 1H),8.78 (d, J=2.4 Hz, 1H), 8.15 (dd, J=8.6, 2.4 Hz, 1H), 7.30 (d, J=2.8 Hz,1H), 7.13 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.8 Hz, 1H), 6.79 (d,J=8.6 Hz, 1H), 6.19 (s, 1H), 4.00 (s, 3H), 3.88 (s, 3H), 2.83 (s, 2H),1.35 (s, 6H).

EXAMPLE 86(15)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-2-yl)ethan-1-one

TLC: Rf0.46 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.94 (br, 1H),8.66 (m, 1H), 8.14 (dt, J=7.8, 1.5 Hz, 1H), 7.82 (dt, J=1.5, 7.8 Hz,1H), 7.49 (d, J=2.6 Hz, 1H), 7.35 (m, 1H), 7.12 (d, J=8.3 Hz, 1H), 7.08(s, 1H), 6.99 (dd, J=8.3, 2.6 Hz, 1H), 3.89 (s, 3H), 2.85 (s, 2H), 1.37(s, 6H).

EXAMPLE 86(16)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-3-yl)ethan-1-one

TLC: Rf0.38 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.87 (br, 1H),9.15 (d, J=1.9 Hz, 1H), 8.67 (dd, J=4.8, 1.9 Hz, 1H), 8.21 (dt, J=7.8,1.9 Hz, 1H), 7.38 (dd, J=7.8, 4.8 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 7.15(d, J=8.5 Hz, 1H), 7.01 (d d, J=8.5, 2.7 Hz, 1H), 6.23 (s, 1H), 3.88 (s,3H), 2.85 (s 2H), 1.37 (s, 6H).

EXAMPLE 86(17)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-iodophenyl)ethan-1-one

TLC: Rf0.52 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 1.35 (s, 6H) 2.84(s, 2H) 3.89 (s, 3H) 6.17 (s, 1H) 7.00 (dd, J=8.24, 2.75 Hz, 1H) 7.14(d, J=8.52 Hz, 1H) 7.17 (t, J=7.69 Hz, 1H) 7.32 (d, J=2.47 Hz, 1H) 7.77(dt, J=7.97, 1.37 Hz, 1H) 7.88 (dt, J=7.76, 1.34 Hz, 1H) 8.26 (t, J=1.65Hz, 1H) 11.85 (s, 1H).

EXAMPLE 86(18)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.10 (br, 1H),8.02 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 7.31 (d, J=2.6 Hz, 1H),7.15 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.6 Hz, 1H), 6.23 (s, 1H), 3.88(s, 3H), 2.85 (s, 2H), 1.72-1.56 (m, 4H), 0.95 (t, J=7.7 Hz, 6H).

EXAMPLE 86(19)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(pyridin-4-yl)ethan-1-one

TLC: Rf0.53 (hexane:ethyl acetate=1:5); NMR (CDCl₃): δ 11.98 (br, 1H),8.72 (dd, J=4.5, 1.5 Hz, 2H), 7.74 (dd, J=4.5, 1.5 Hz, 2H), 7.32 (d,J=2.7 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 7.02 (dd, J=8.3, 2.7 Hz, 1H),6.23 (s, 1H), 3.89 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 86(20)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-cyanophenyl)ethan-1-one

TLC: Rf0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.06 (br, 1H),8.22 (t, J=1.7 Hz, 1H), 8.17 (dt, J=8.0, 1.7 Hz, 1H), 7.71 (dt, J=8.0,1.7 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.31 (d, J=2.7 Hz, 1H), 7.15 (d,J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.7 Hz, 1H), 6.21 (s, 1H), 3.89 (s, 3H),2.85 (s, 2H), 1.75-1.55 (m, 4H), 0.95 (t, J=7.5 Hz, 6H).

EXAMPLE 86(21)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-cyanophenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 0.65 (t, J=7.2Hz, 6H), 1.96 (m, 4H), 3.93 (s, 3H), 6.27 (s, 1H), 7.12 (dd, J=8.4, 2.4Hz, 1H), 7.24 (d, J=2.4 Hz, 1H), 7.23 (d, J=8.4 Hz, 1H), 7.57 (t, J=7.5Hz, 1H), 7.74 (dt, J=7.5, 1.8 Hz, 1H), 8.24 (dt, J=7.5, 1.8 Hz, 1H),8.29 (t, J=1.8 Hz, 1H), 10.35 (s, 1H).

EXAMPLE 86(22)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-(pyrrolidin-1-yl)phenyl)ethan-1-one

TLC: Rf0.19 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 1.55 (s, 6H),2.03 (m, 4H), 3.38 (t, J=6.6 Hz, 4H), 3.90 (s, 3H), 6.31 (s, 1H), 6.57(d, J=8.7 Hz, 2H), 7.05 (dd, J=8.4, 2.4 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H),7.28 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.7 Hz, 2H), 10.22 (s, 1H).

EXAMPLE 86(23)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-cyanophenyl)ethan-1-one

TLC: Rf0.21 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 1.59 (s, 6H),3.93 (s, 3H), 6.26 (s, 1H), 7.12 (dd, J=8.4, 2.4 Hz, 1H), 7.23 (d, J=2.4Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.74 (dt,J=7.5, 1.5 Hz, 1H), 8.22 (dt, J=7.5, 1.5 Hz, 1H), 8.28 (t, J=1.5 Hz,1H), 10.49 (s, 1H).

EXAMPLE 86(24)(Z)-2-(7-methoxy-3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 1.37 (s, 6H) 2.31(s, 3H) 2.78 (s, 2H) 3.87 (s, 3H) 6.20 (s, 1H) 6.92 (d, J=2.20 Hz, 1H)7.18 (d, J=2.20 Hz, 1H) 7.72 (d, J=8.24 Hz, 2H) 8.00 (d, J=8.24 Hz, 2H)12.03 (s, 1H).

EXAMPLE 86(25)(Z)-2-(7-methoxy-3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 1.35 (s, 6H) 2.30(s, 3H) 2.75 (s, 2H) 3.86 (s, 3H) 3.87 (s, 3H) 6.23 (s, 1H) 6.88 (d,J=2.75 Hz, 1H) 6.93 (d, J=9.07 Hz, 2H) 7.21 (d, J=2.75 Hz, 1H) 7.93 (d,J=9.07 Hz, 2H) 11.82 (s, 1H).

EXAMPLE 86(26)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-dimethylaminophenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.55 (s, 6H),3.05 (s, 6H), 3.90 (s, 3H), 6.30 (s, 1H), 6.73 (d, J=8.7 Hz, 2H), 7.06(dd, J=8.7, 2.4 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H), 7.28 (d, J=8.7 Hz, 1H),7.96 (d, J=8.7 Hz, 2H), 10.24 (s, 1H).

EXAMPLE 86(27)(Z)-2-(7-methoxy-3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 1.38 (s, 6H) 2.32(s, 3H) 2.79 (s, 2H) 3.88 (s, 3H) 6.22 (s, 1H) 6.93 (d, J=2.75 Hz, 1H)7.20 (d, J=2.75 Hz, 1H) 8.06 (d, J=8.79 Hz, 2H) 8.28 (d, J=8.79 Hz, 2H)12.07 (s, 1H).

EXAMPLE 87-EXAMPLE 87(6)

By the same procedure as described in example 58 using the compoundprepared in example 86(8), 86(4), 86(5), 86(12), 86(9)_(m 86)(13) or86(27) in place of the compound prepared in example 56, the followingcompounds of the present invention were given.

EXAMPLE 87(Z)-2-(6-methoxy-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzothiazin-4-ylidene)-1-(4-aminophenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 12.21 (s, 1H),7.80 (d, J=8.7 Hz, 2H), 7.33 (d, J=2.7 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H),6.97 (dd, J=8.7, 2.7 Hz, 1H), 6.68 (d, J=8.7 Hz, 2H), 6.16 (s, 1H), 3.96(br s, 2H), 3.89 (s, 3H), 1.71 (s, 6H).

EXAMPLE 87(1)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-aminophenyl)ethan-1-one

TLC: Rf0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.13 (br, s,1H), 7.89 (d, J=9.0 Hz, 2H), 7.21 (d, J=2.1 Hz, 1H), 7.19 (d, J=8.7 Hz,1H), 7.06 (dd, J=8.7, 2.1 Hz, 1H), 6.71 (d, J=9.0 Hz, 2H), 6.28 (s, 1H),3.93 (br, s, 2H), 3.90 (s, 3H), 2.05-1.80 (m, 4H), 0.64 (t, J=7.5 Hz,6H).

EXAMPLE 87(2)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-aminophenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.24 (br, s,1H), 7.40 (m, 1H), 7.35 (m, 1H), 7.30-7.15 (m, 3H), 7.07 (dd, J=8.7, 2.1Hz, 1H), 6.79 (m, 1H), 6.29 (s, 1H), 3.90 (s, 3H), 3.76 (br, s, 2H),2.05-1.80 (m, 4H), 0.65 (t, J=7.5 Hz, 6H).

EXAMPLE 87(3)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-aminophenyl)ethan-1-one

TLC: Rf0.58 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 10.37 (br, s,1H), 7.38 (m, 1H), 7.33 (m, 1H), 7.29 (d, J=8.4 Hz, 1H), 7.23 (t, J=7.5Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 7.08 (dd, J=8.4, 2.1 Hz, 1H), 6.79(ddd, J=7.5, 2.4, 1.5 Hz, 1H), 6.28 (s, 1H), 3.90 (s, 3H), 3.77 (br, s,2H), 1.56 (s, 6H).

EXAMPLE 87(4)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-aminophenyl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.80 (br, 1H),7.83 (d, J=8.6 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H), 7.11 (d, J=8.4 Hz, 1H),6.95 (dd, J=8.4, 2.6 Hz, 1H), 6.69 (d, J=8.6 Hz, 2H), 6.25 (s, 1H), 3.91(s, 2H), 3.87 (s, 3H), 2.80 (s, 2H), 1.70-1.50 (m, 4H), 0.92 (t, J=7.5Hz, 6H).

EXAMPLE 87(5)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-aminophenyl)ethan-1-one

TLC: Rf0.63 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.95 (br, 1H),7.35-7.28 (m, 3H), 7.21 (t, J=7.7 Hz, 1H), 7.12 (d, J=8.5 Hz, 1H), 6.97(dd, J=8.5, 2.6 Hz, 1H), 6.77 (m, 1H), 6.26 (s, 1H), 3.87 (s, 3H), 3.74(br, 2H), 2.82 (s, 2H), 1.70-1.53 (m, 4H), 0.93 (t, J=7.5 Hz, 6H).

EXAMPLE 87(6)(Z)-2-(7-methoxy-3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-aminophenyl)ethan-1-one

TLC: Rf0.32 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.32 (s, 6H) 2.28(s, 3H) 2.72 (s, 2H) 3.85 (s, 3H) 3.89 (s, 2H) 6.20 (s, H) 6.67 (d,J=8.79 Hz, 2H) 6.85 (d, J=2.75 Hz, 1H) 7.19 (d, J=2.75 Hz, 1H) 7.80 (d,J=8.79 Hz, 2H) 11.73 (s, 1H).

EXAMPLE 88-EXAMPLE 88(1)

By the same procedure as described in example 79 using the compoundprepared in example 86(24) and example 56(1) in place of the compoundprepared in example 79, the compounds of the present invention havingthe following physical data were given.

EXAMPLE 88(Z)-2-(7-methoxy-3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-carboxyphenyl)ethan-1-one

TLC: Rf0.47 (chloroform:methanol=10:1); NMR (DMSO-d₆): δ 1.29 (s, 6H)2.28 (s, 3H) 2.78 (s, 2H) 3.84 (s, 3H) 6.44 (s, 1H) 7.03 (d, J=2.47 Hz,1H) 7.40 (d, J=2.47 Hz, 1H) 7.99 (m, 3H) 8.09 (d, J=8.79 Hz, 2H) 12.08(s, 1H).

EXAMPLE 88(1)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-carboxyphenyl)ethan-1-one

TLC: Rf0.52 (ethyl acetate); NMR (DMSO-d₆): δ 1.52 (s, 6H), 3.86 (s,3H), 6.64 (s, 1H), 7.14 (dd, J=8.39, 2.35 Hz, 1H), 7.51 (d, J=8.39 Hz,1H), 7.65 (d, J=2.35 Hz, 1H), 8.02 (d, J=8.06 Hz, 2H), 8.13 (d, J=8.06Hz, 2H), 10.49 (s, 1H), 13.09 (s, 1H).

EXAMPLE 89-EXAMPLE 89(26)

By the same procedure as described in example 68 using the compoundprepared in example 66(1) or a corresponding derivative instead, and acorresponding derivative in place of 2-hydroxy-1,1-dimethylethylamine,the compounds of the present invention having the following physicaldata were given.

EXAMPLE 89(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(1,1-dioxotetrahydrothiophen-3-ylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.57 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.92 (br, 1H),8.28 (m, 1H), 8.09 (m, 1H), 7.91 (m, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.34(d, J=2.6 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.01 (dd, J=8.3, 2.6 Hz, 1H),6.82 (d, J=7.8 Hz, 1H), 6.27 (s, 1H), 5.00 (m, 1H), 3.89 (s, 3H), 3.52(dd, J=13.8, 7.2 Hz, 1H), 3.32 (m, 1H), 3.24-3.08 (m, 2H), 2.85 (s, 2H),2.65 (m, 1H), 2.42 (m, 1H), 1.37 (s, 6H).

EXAMPLE 89(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(1,1-dioxotetrahydrothiophen-3-ylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.52 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.94 (br, 1H),8.00 (d, J=8.1 Hz, 2H), 7.83 (d, J=8.1 Hz, 2H), 7.33 (d, J=2.6 Hz, 1H),7.15 (d, J=8.5 Hz, 1H), 7.01 (dd, J=8.5, 2.6 Hz, 1H), 6.80 (d, J=7.8 Hz,1H), 6.26 (s, 1H), 5.04 (m, 1H), 3.89 (s, 3H), 3.47 (dd, J=13.8, 6.9 Hz,1H), 3.37-3.10 (m, 3H), 2.85 (s, 2H), 2.64 (m, 1H), 2.46 (m, 1H), 1.36(s, 6H).

EXAMPLE 89(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(morpholin-4-yl)ethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.47 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.90 (br, s,1H), 8.31 (m, 1H), 8.07 (m, 1H), 7.91 (m, 1H), 7.52 (t, J=7.8 Hz, 1H),7.35 (d, J=2.4 Hz, 1H), 7.15 (d, J=8.1 Hz, 1H), 7.00 (dd, J=8.1, 2.4 Hz,1H), 6.81 (m, 1H), 6.29 (s, 1H), 3.88 (s, 3H), 3.78-3.66 (m, 4H),3.62-3.56 (m, 2H), 2.85 (s, 2H), 2.64-2.58 (m, 2H), 2.56-2.44 (m, 4H),1.37 (s, 6H).

EXAMPLE 89(3)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(pyridin-4-ylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.46 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.93 (br, s,1H), 8.60-8.52 (m, 2H), 8.44-8.36 (m, 2H), 8.12-8.00 (m, 2H), 7.72-7.62(m, 2H), 7.56 (t, J=8.1 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.15 (d, J=8.1Hz, 1H), 7.01 (dd, J=8.1, 2.4 Hz, 1H), 6.28 (s, 1H), 3.88 (s, 3H), 2.83(s, 2H), 1.36 (s, 6H).

EXAMPLE 89(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(2-hydroxyethoxy)ethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.46 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.89 (br, s,1H), 8.34 (m, 1H), 8.04 (m, 1H), 7.97 (m, 1H), 7.50 (t, J=8.4 Hz, 1H),7.35 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.4 Hz,1H), 6.97 (m, 1H), 6.29 (s, 1H), 3.88 (s, 3H), 3.82-3.76 (m, 2H),3.76-3.60 (m, 6H), 2.84 (s, 2H), 2.60 (br, s, 1H), 1.36 (s, 6H).

EXAMPLE 89(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((tetrahydrofuran-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.58 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.90 (br, s,1H), 8.32 (m, 1H), 8.06 (m, 1H), 7.94 (m, 1H), 7.51 (t, J=8.4 Hz, 1H),7.34 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.4 Hz,1H), 6.63 (m, 1H), 6.29 (s, 1H), 4.08 (m, 1H), 3.96-3.74 (m, 3H), 3.88(s, 3H), 3.38 (m, 1H), 2.84 (s, 2H), 2.10-1.84 (m, 3H), 1.62 (m, 1H),1.36 (s, 6H).

EXAMPLE 89(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-ethoxycarbonylpiperidin-4-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.53 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.92 (br, s,1H), 8.25 (m, 1H), 8.04 (m, 1H), 7.96 (m, 1H), 7.52 (t, J=8.4 Hz, 1H),7.34 (d, J=2.4 Hz, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4, 2.4 Hz,1H), 6.28 (s, 1H), 6.16 (d, J=8.1 Hz, 1H), 4.15 (m, 1H), 4.15 (q, J=7.2Hz, 2H), 3.89 (s, 3H), 3.02-2.86 (m, 2H), 2.85 (s, 2H), 2.12-1.98 (m,2H), 1.54-1.38 (m, 4H), 1.37 (s, 6H), 1.28 (t, J=7.2 Hz, 3H).

EXAMPLE 89(7)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.44 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.91 (br, s,1H), 8.32 (m, 1H), 8.06 (m, 1H), 7.95 (m, 1H), 7.51 (t, J=8.4 Hz, 1H),7.34 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.4 Hz,1H), 6.64 (m, 1H), 6.29 (s, 1H), 3.88 (s, 3H), 3.72-3.62 (m, 2H),3.60-3.52 (m, 2H), 3.39 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 89(8)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methylpiperazin-1-ylcarbonyl)phenyl)ethan-1-one

TLC: Rf0.49 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.86 (br, s,1H), 8.04-7.88 (m, 2H), 7.56-7.42 (m, 2H), 7.32 (d, J=2.4 Hz, 1H), 7.14(d, J=8.7 Hz, 1H), 7.00 (dd, J=8.7, 2.4 Hz, 1H), 6.25 (s, 1H), 3.94-3.70(m, 2H), 3.88 (s, 3H), 3.56-3.36 (m, 2H), 2.84 (s, 2H), 2.60-2.18 (m,4H), 2.32 (s, 3H), 1.36 (s, 6H).

EXAMPLE 89(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.54 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.90 (br, s,1H), 8.59 (m, 1H), 8.42 (m, 1H), 8.08 (m, 1H), 8.00 (m, 1H), 7.69 (m,1H), 7.63 (br, s, 1H), 7.56 (t, J=8.4 Hz, 1H), 7.40-7.31 (m, 2H), 7.22(m, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H), 6.31 (s,1H), 4.80 (d, J=5.1 Hz, 2H), 3.88 (s, 3H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 89(10)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(piperidin-1-yl)ethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.19 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.90 (br, s,1H), 8.33 (m, 1H), 8.07 (m, 1H), 7.90 (m, 1H), 7.51 (t, J=8.4 Hz, 1H),7.35 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.4 Hz,1H), 7.00 (m, 1H), 6.31 (s, 1H), 3.88 (s, 3H), 3.57 (q, J=6.0 Hz, 2H),2.84 (s, 2H), 2.57 (t, J=6.0 Hz, 2H), 2.52-2.36 (m, 4H), 1.76-1.50 (m,4H), 1.50-1.38 (m, 2H), 1.37 (s, 6H).

EXAMPLE 89(11)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-oxidopyridin-2-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.59 (chloroform:methanol=10:1); NMR (CDCl₃): δ 11.92 (br, s,1H), 10.97 (br, s, 1H), 8.64 (dd, J=8.7, 2.1 Hz, 1H), 8.56 (m, 1H), 8.31(dd, J=6.9, 1.5 Hz, 1H), 8.19 (m, 1H), 8.06 (m, 1H), 7.61 (t, J=8.4 Hz,1H), 7.40 (m, 1H), 7.36 (d, J=2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H),7.08-6.98 (m, 2H), 6.31 (s, 1H), 3.90 (s, 3H), 2.85 (s, 2H), 1.37 (s,6H).

EXAMPLE 89(12)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(ethylcarbamoyl)phenyl)ethan-1-one

TLC: Rf0.43 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.27 (t, J=7.2Hz, 3H), 1.36 (s, 6H), 2.85 (s, 2H), 3.53 (m, 2H), 3.89 (s, 3H), 6.25(m, 1H), 6.29 (s, 1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H), 7.15 (d, J=8.4 Hz,1H), 7.35 (d, J=2.4 Hz, 1H), 7.51 (t, J=8.4 Hz, 1H), 7.93 (m, 1H), 8.04(m, 1H), 8.28 (m, 1H), 11.92 (s, 1H).

EXAMPLE 89(13)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(((1S)-1-hydroxymethyl-3-methylthiopropyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.31 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.36 (s, 6H),1.99 (m, 2H), 2.13 (s, 3H), 2.63 (t, J=7.2 Hz, 2H), 2.74 (t, J=5.4 Hz,1H), 2.84 (s, 2H), 3.80 (m, 2H), 3.88 (s, 3H), 4.32 (m, 1H), 6.28 (s,1H), 6.77 (d, J=7.8 Hz, 1H), 7.00 (d d, J=8.7, 2.7 Hz, 1H), 7.14 (d,J=8.7 Hz, 1H), 7.34 (d, J=2.7 Hz, 1H), 7.51 (t, J=8.7 Hz, 1H), 7.95 (m,1H), 8.06 (m, 1H), 8.32 (m, 1H), 11.90 (s, 1H).

EXAMPLE 89(14)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-oxidopyridin-2-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.50 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.38 (s, 6H),2.86 (s, 2H), 3.89 (s, 3H), 6.29 (s, 1H), 7.04 (m, 2H), 7.15 (d, J=8.4Hz, 1H), 7.35 (d, J=3.0 Hz, 1H), 7.42 (m, 1H), 8.08 (s, 4H), 8.32 (m,1H), 8.64 (m, 1H), 10.99 (s, 1H), 11.97 (s, 1H).

EXAMPLE 89(15)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-dimethylaminoethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.15 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.37 (s, 6H),2.27 (s, 6H), 2.53 (t, J=5.7 Hz, 2H), 2.85 (s, 2H), 3.55 (m, 2H), 3.88(s, 3H), 6.30 (s, 1H), 6.90 (m, 1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H), 7.14(d, J=8.4 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 7.94(m, 1H), 8.06 (m, 1H), 8.33 (m, 1H), 11.89 (s, 1H).

EXAMPLE 89(16)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(acetylamino)ethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.50 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.36 (s, 6H),2.01 (s, 3H), 2.84 (s, 2H), 3.52 (m, 2H), 3.62 (m, 2H), 3.87 (s, 3H),6.29 (m, 1H), 6.36 (s, 1H), 6.99 (dd, J=8.4, 2.4 Hz, 1H), 7.14 (d, J=8.4Hz, 1H), 7.30 (m, 1H), 7.44 (d, J=2.4 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H),7.93 (dt, J=7.8, 1.6 Hz, 1H), 8.09 (dt, J=7.8, 1.6 Hz, 1H), 8.35 (t,J=1.6 Hz, 1H), 11.94 (s, 1H).

EXAMPLE 89(17)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-(2-hydroxyethyl)piperazin-1-ylcarbonyl)phenyl)ethan-1-one

TLC: Rf0.48 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.36 (s, 6H),2.51 (m, 5H), 2.60 (t, J=5.4 Hz, 2H), 2.84 (s, 2H), 3.48 (m, 2H), 3.65(t, J=5.4 Hz, 2H), 3.84 (m, 2H), 3.88 (s, 3H), 6.24 (s, 1H), 7.00 (dd,J=8.7, 2.4 Hz, 1H), 7.14 (d, J=8.7 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 7.49(m, 2H), 7.94 (m, 1H), 7.99 (m, 1H), 11.86 (s, 1H).

EXAMPLE 89(18)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-3-ylmethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.11 (ethyl acetate); NMR (CDCl₃): δ 1.35 (s, 6H), 2.84 (s, 2H),3.88 (s, 3H), 4.69 (d, J=6.0 Hz, 2H), 6.28 (s, 1H), 6.71 (t, J=6.0 Hz,1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.29 (m, 1H),7.33 (d, J=2.4 Hz, 1H), 7.53 (t, J=7.8 Hz, 1H), 7.73 (m, 1H), 7.98 (dt,J=7.8, 1.8 Hz, 1H), 8.07 (dt, J=7.8, 1.8 Hz, 1H), 8.30 (t, J=1.8 Hz,1H), 8.55 (m, 1H), 8.63 (m, 1H), 11.91 (s, 1H).

EXAMPLE 89(19)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-dimethylaminopropyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.21 (ethyl acetate:methanol:ammonia water=50:10:1); NMR (CDCl₃):δ 1.36 (s, 6H), 1.78 (m, 2H), 2.31 (s, 6H), 2.50 (m, 2H), 2.84 (s, 2H),3.59 (m, 2H), 3.88 (s, 3H), 6.30 (s, 1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H),7.14 (d, J=8.4 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H),7.89 (dt, J=7.8, 1.8 Hz, 1H), 8.06 (dt, J=7.8, 1.8 Hz, 1H), 8.33 (t,J=1.8 Hz, 1H), 8.40 (m, 1H), 11.90 (s, 1H).

EXAMPLE 89(20)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl)phenyl)ethan-1-one

TLC: Rf0.19 (ethyl acetate); NMR (CDCl₃): δ 1.36 (s 6H), 1.74 (m, 3H),2.19 (m, 1H), 2.84 (s, 2H), 3.52 (m, 2H), 3.80 (m, 2H), 3.89 (s, 3H),4.42 (m, 1H), 4.93 (m, 1H), 6.25 (s, 1H), 7.00 (dd, J=8.4, 2.7 Hz, 1H),7.15 (d, J=8.4 Hz, 1H), 7.34 (d, J=2.7 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H),7.60 (m, 1H), 8.01 (m, 1H), 8.06 (m, 1H), 11.89 (s, 1H).

EXAMPLE 89(21)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,6-dimethylmorpholin-1-ylcarbonyl)phenyl)ethan-1-one

TLC: Rf0.56 (ethyl acetate); NMR (CDCl₃): δ 1.09 (s, 3H), 1.25 (s, 3H),1.36 (s, 3H), 2.58 (m, 1H), 2.83 (s, 2H), 2.83 (m, 1H), 3.60 (m, 3H),3.88 (s, 3H), 4.61 (m, 1H), 6.24 (s, 1H), 7.00 (dd, J=8.4, 2.4 Hz, 1H),7.14 (d, J=8.4 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 7.49 (m, 2H), 7.92 (m,1H), 8.00 (m, 1H), 11.87 (s, 1H).

EXAMPLE 89(22)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-ethylpyrrolidin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.48 (ethyl acetate:methanol:ammonia water=50:10:1); NMR (CDCl₃):δ 1.14 (t, J=7.2 Hz, 3H), 1.37 (s, 6H), 1.72 (m, 3H), 1.93 (m, 1H), 2.26(m, 2H), 2.71 (m, 1H), 2.84 (s, 2H), 2.86 (m, 1H), 3.22 (m, 1H), 3.34(m, 1H), 3.76 (m, 1H), 3.88 (s, 3H), 6.31 (s, 1H), 6.91 (m, 1H), 7.00(dd, J=8.4, 2.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H),7.52 (t, J=7.8 Hz, 1H), 7.90 (m, 1H), 8.08 (m, 1H), 8.33 (m, 1H), 11.90(s, 1H).

EXAMPLE 89(23)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-2-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.37 (s, 6H),2.85 (s, 2H), 3.89 (s, 3H), 6.29 (s, 1H), 7.01 (dd, J=8.4, 2.4 Hz, 1H),7.09 (m, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.78 (m,1H), 7.99 (d, J=8.1 Hz, 2H), 8.06 (d, J=8.1 Hz, 2H), 8.33 (m, 1H), 8.41(m, 1H), 8.61 (s, 1H), 11.96(s, 1H).

EXAMPLE 89(24)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((2-(morpholin-4-yl)ethyl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.26 (ethyl acetate:methanol=10:1); NMR (CDCl₃): δ 1.58 (s, 6H),2.52 (m, 4H), 2.63 (m, 2H), 3.58 (m, 2H), 3.75 (m, 4H), 3.91 (s, 3H),6.33 (s, 1H), 6.83 (m, 1H), 7.11 (dd, J=8.24, 2.47 Hz, 1H), 7.22 (d,J=2.47 Hz, 1H), 7.32 (d, J=8.24 Hz, 1H), 7.86 (d, J=8.24 Hz, 2H), 8.06(d, J=8.24 Hz, 2H), 10.51 (s, 1H).

EXAMPLE 89(25)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((1-oxidopyridin-2-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.24 (ethyl acetate); NMR (CDCl₃): δ 1.58 (s, 6H), 3.92 (s, 3H),6.35 (s, 1H), 7.05 (m, 1H), 7.12 (dd, J=8.24, 2.47 Hz, 1H), 7.24 (d,J=2.47 Hz, 1H), 7.32 (d, J=8.24 Hz, 1H), 7.42 (m, 1H), 8.12 (m, 4H),8.32 (m, 1H), 8.64 (dd, J=8.52, 1.92 Hz, 1H), 10.56 (s, 1H), 11.00 (s,1H).

EXAMPLE 89(26)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((pyridin-4-yl)carbamoyl)phenyl)ethan-1-one

TLC: Rf0.30 (ethyl acetate); NMR (CDCl₃): δ 1.58 (s, 6H), 3.91 (s, 3H),6.32 (s, 1H), 7.12 (dd, J=8.24, 2.20 Hz, 1H), 7.23 (d, J=2.20 Hz, 1H),7.33 (d, J=8.24 Hz, 1H), 7.66 (m, 2H), 7.94 (d, J=8.52 Hz, 2H), 8.08 (d,J=8.52 Hz, 2H), 8.21 (s, 1H), 8.58 (m, 2H), 10.53 (s, 1H).

EXAMPLE 90-EXAMPLE 90(16)

By the same procedure as described in example 63 using a correspondingderivative in place of the compound prepared in example 62 and theacetic anhydride or a corresponding acid anhydride, acid halide orsulfonyl halide instead, optionally followed by converting to acorresponding salt, the following compounds of the present inventionwere given.

EXAMPLE 90(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methylthiopropanoyl)amino)phenyl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.82 (br, 1H),7.94 (m, 1H), 7.80 (m, 1H), 7.69-7.65 (m, 2H), 7.40 (t, J=7.0 Hz, 1H),7.34 (d, J=2.5 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 6.99 (dd, J=8.3, 2.5 Hz,1H), 6.25 (s, 1H), 3.88 (s, 3H), 2.91 (t, J=7.0 Hz, 2H), 2.83 (s, 2H),2.68 (t, J=7.0 Hz, 2H), 2.18 (s, 3H), 1.35 (s, 6H).

EXAMPLE 90(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(4-methoxyphenyl)acetyl)amino)phenyl)ethan-1-one

TLC: Rf0.61 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 11.82 (br, 1H),7.98 (m, 1H), 7.62 (m, 1H), 7.54 (m, 1H), 7.37 (t, J=8.0 Hz, 1H), 7.31(d, J=2.5 Hz, 1H), 7.25 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 1H), 7.13(br, 1H), 6.99 (dd, J=8.4, 2.5 Hz, 1H), 6.94 (d, J=8.4 Hz, 2H), 6.22 (s,1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.71 (s, 2H), 2.82 (s, 2H), 1.33 (s,6H).

EXAMPLE 90(2)(Z)-2-(6-methoxy-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzothiazin-4-ylidene)-1-(4-(acetylamino)phenyl)ethan-1-one

TLC: Rf0.58 (ethyl acetate); NMR (CDCl₃): δ 12.34 (s, 1H), 7.91 (d,J=8.7 Hz, 2H), 7.58 (d, J=8.7 Hz, 2H), 7.34 (d, J=2.7 Hz, 1H), 7.27 (d,J=8.7 Hz, 1H), 7.26 (m, 1H), 7.00 (dd, J=8.7, 2.7 Hz, 1H), 6.19 (s, 1H),3.89 (s, 3H), 2.21 (s, 3H), 1.72 (s, 6H).

EXAMPLE 90(3)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-onehydrochloride

TLC: Rf0.35 (ethyl acetate); NMR (DMSO-d₆): δ 10.87 (br s, 1H), 10.17(s, 1H), 8.94 (m, 2H), 8.36 (s, 1H), 8.18 (m, 2H), 7.97 (d, J=7.8 Hz,1H), 7.87 (d, J=7.8 Hz, 1H), 7.59 (d, J=2.1 Hz, 1H), 7.50 (t, J=7.8 Hz,1H), 7.40 (d, J=8.4 Hz, 1H), 7.14 (dd, J=8.4, 2.1 Hz, 1H), 6.56 (s, 1H),6.00-4.00 (br s, 1H), 3.86 (s, 3H), 2.10-1.85 (m, 4H), 0.48 (t, J=7.2Hz, 6H).

EXAMPLE 90(4)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.35 (ethyl acetate); NMR (CDCl₃): δ 10.29 (s, 1H), 8.83 (d,J=5.4 Hz, 2H), 8.07 (d, J=8.1 Hz, 2H), 8.02 (s, 1H), 7.77-7.73 (m, 4H),7.24-7.20 (m, 2H), 7.09 (dd, J=8.7, 2.4 Hz, 1H), 6.34 (s, 1H), 3.92 (s,3H), 2.01-1.84 (m, 4H), 0.65 (t, J=7.2 Hz, 6H).

EXAMPLE 90(5)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.24 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.27 (br, s,1H), 8.38 (br, s, 1H), 8.02 (d, J=8.7 Hz, 2H), 7.68 (d, J=8.7 Hz, 2H),7.23 (d, J=2.7 Hz, 1H), 7.21 (d, J=8.1 Hz, 1H), 7.08 (dd, J=8.1, 2.7 Hz,1H), 6.32 (s, 1H), 4.04 (s, 2H), 3.91 (s, 3H), 3.53 (s, 3H), 2.05-1.80(m, 4H), 0.65 (t, J=7.5 Hz, 6H).

EXAMPLE 90(6)(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.40 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.32 (br, s,1H), 8.38 (br, s, 1H), 8.00-7.90 (m, 2H), 7.77 (m, 1H), 7.44 (t, J=8.1Hz, 1H), 7.30-7.15 (m, 2H), 7.09 (dd, J=8.4, 2.1 Hz, 1H), 6.31 (s, 1H),4.05 (s, 2H), 3.91 (s, 3H), 3.53 (s, 3H), 2.05-1.80 (m, 4H), 0.66 (t,J=7.4 Hz, 6H).

EXAMPLE 90(7)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.26 (ethyl acetate); NMR (CDCl₃): δ 10.42 (br, s, 1H), 8.82 (d,J=6.0 Hz, 2H), 8.07 (br, s, 1H), 8.06 (d, J=8.7 Hz, 2H), 7.76 (d, J=8.7Hz, 2H), 7.74 (d, J=6.0 Hz, 2H), 7.31 (d, J=8.1 Hz, 1H), 7.23 (d, J=2.4Hz, 1H), 7.10 (dd, J=8.1, 2.4 Hz, 1H), 6.33 (s, 1H), 3.91 (s, 3H), 1.57(s, 6H).

EXAMPLE 90(8)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.35 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 10.40 (br, s,1H), 8.38 (br, s, 1H), 8.01 (d, J=8.7 Hz, 2H), 7.68 (d, J=8.7 Hz, 2H),7.30 (d, J=8.1 Hz, 1H), 7.22 (d, J=2.7 Hz, 1H), 7.09 (dd, J=8.1, 2.7 Hz,1H), 6.31 (s, 1H), 4.04 (s, 2H), 3.91 (s, 3H), 3.53 (s, 3H), 1.57 (s,6H).

EXAMPLE 90(9)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.26 (ethyl acetate); NMR (CDCl₃): δ 1.57 (s, 6H) 3.91 (s, 3H)6.33 (s, 1H) 7.10 (dd, J=8.52, 2.47 Hz, 1H) 7.23 (d, J=2.47 Hz, 1H) 7.31(d, J=8.52 Hz, 1H) 7.50 (t, J=8.24 Hz, 1H) 7.74 (d, J=5.22 Hz, 2H) 7.82(m, 1H) 8.05 (m, 3H) 8.82 (d, J=5.22 Hz, 2H) 10.44 (s, 1H).

EXAMPLE 90(10)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.45 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 1.58 (s, 6H) 3.54(s, 3H) 3.91 (s, 3H) 4.05 (s, 2H) 6.31 (s, 1H) 7.09 (dd, J=8.24, 2.47Hz, 1H) 7.23 (d, J=2.47 Hz, 1H) 7.30 (d, J=8.24 Hz, 1H) 7.44 (t, J=7.69Hz, 1H) 7.76 (m, 1H) 7.95 (m, 2H) 8.38 (s, 1H) 10.44 (s, 1H).

EXAMPLE 90(11)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(3-acetylaminophenyl)ethan-1-one

TLC: Rf0.25 (chloroform:methanol=10:1); NMR (CDCl₃): δ 1.57 (s, 6H),2.21 (s, 3H), 3.90 (s, 3H), 6.30 (s, 1H), 7.09 (dd, J=8.4, 2.4 Hz, 1H),7.22 (d, J=2.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.39 (s, 1H), 7.42 (t,J=7.8 Hz, 1H), 7.73 (m, 1H), 7.89 (m, 2H), 10.43 (s, 1H).

EXAMPLE 90(12)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.28 (ethyl acetate); NMR (CDCl₃): δ 0.94 (t, J=7.2 Hz, 6H), 1.64(m, 4H), 2.84 (s, 2H), 3.88 (s, 3H), 6.29 (s, 1H), 6.99 (dd, J=8.4, 2.4Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.48 (t, J=8.1Hz, 1H), 7.74 (m, 3H), 7.95 (m, 2H), 8.08 (m, 1H), 8.83 (m, 2H), 12.03(s, 1H).

EXAMPLE 90(13)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-4-ylcarbonyl)amino)phenyl)ethan-1-one

TLC: Rf0.22 (ethyl acetate); NMR (CDCl₃): δ 0.94 (t, J=7.2 Hz, 6H), 1.64(m, 4H), 2.83 (s, 2H), 3.89 (s, 3H), 6.29 (s, 1H), 6.99 (dd, J=8.4, 2.4Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.74 (m, 4H),7.96 (m, 1H), 8.02 (m, 2H), 8.83 (m, 2H), 11.98 (s, 1H).

EXAMPLE 90(14)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.27 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 0.94 (t, J=7.5Hz, 6H), 1.63 (m, 4H), 2.83 (s, 2H), 3.52 (s, 3H), 3.88 (s, 3H), 4.03(s, 2H), 6.28 (s, 1H), 6.98 (dd, J=8.4, 2.4 Hz, 1H), 7.13 (d, J=8.4 Hz,1H), 7.34 (d, J=2.4 Hz, 1H), 7.42 (t, J=7.8 Hz, 1H), 7.70 (dt, J=7.8,1.8 Hz, 1H), 7.86 (t, J=1.8 Hz, 1H), 8.02 (dt, J=7.8, 1.8 Hz, 1H), 8.38(s, 1H), 12.03 (s, 1H).

EXAMPLE 90(15)(Z)-2-(7-methoxy-3,3-diethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methoxyacetyl)amino)phenyl)ethan-1-one

TLC: Rf0.22 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 0.92 (t, J=7.2Hz, 6H), 1.62 (m, 4H), 2.82 (s, 2H), 3.52 (s, 3H), 3.88 (s, 3H), 4.03(s, 2H), 6.28 (s, 1H), 6.98 (dd, J=8.4, 2.4 Hz, 1H), 7.12 (d, J=8.4 Hz,1H), 7.33 (d, J=2.4 Hz, 1H), 7.66 (d, J=8.4 Hz, 2H), 7.96 (d, J=8.4 Hz,2H), 8.37 (s, 1H), 11.94 (s, 1H).

EXAMPLE 90(16)(Z)-2-(6-methoxy-3,3-dimethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-mesylaminophenyl)ethan-1-one

TLC: Rf0.39 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.57 (s, 6H) 3.07(s, 3H) 3.91 (s, 3H) 6.27 (s, 1H) 6.58 (s, 1H) 7.10 (dd, J=8.38, 2.34Hz, 1H) 7.21 (d, J=2.34 Hz, 1H) 7.27 (d, J=8.79 Hz, 2H) 7.31 (d, J=8.38Hz, 1H) 8.01 (d, J=8.79 Hz, 2H) 10.41 (s, 1H).

EXAMPLE 91(Z)-2-(6-methoxy-3,3-diethyl-2,3-dihydro-(2H)-isoindol-1-ylidene)-1-(4-dimethylaminophenyl)ethan-1-one

By the same procedure as described in example 41 using the compoundprepared in example 87(1) in place of the compound prepared in example38, the compound of the present invention having the following physicaldata was given.

TLC: Rf0.19 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 0.65 (t, J=7.5Hz, 6H), 1.91 (m, 4H), 3.05 (s, 6H), 3.91 (s, 3H), 6.31 (s, 1H), 6.73(d, J=8.7 Hz, 2H), 7.05 (dd, J=8.4, 2.4 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H),7.22 (d, J=2.4 Hz, 1H), 7.97 (d, J=8.7 Hz, 2H), 10.11 (s, 1H).

EXAMPLE 92(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-(pyridin-4-yl)ethynyl)phenyl)ethan-1-one

To triethylamine (3 ml) was suspended the compound prepared in example86(17) (0.51 g) and the atmosphere was substituted with argon, theretowere added bis(triphenylphosphine)palladium(II) chloride (0.07 g) andcopper bromide(I) (0.02 g) and the atmosphere was again substituted withargon, thereto was added 4-ethynylpyridine (0.13 g) and the mixture wasstirred for 1 hour at 60° C. and for 4 hours at 90° C. The reactionmixture was azeotroped with toluene. To the residue was added water andethyl acetate and was filtered. The filtrate was washed with water andbrine, dried over anhydrous magnesium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=1:1) to give the compound of the present invention(0.44 g) having the following physical data.

TLC: Rf0.49 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 11.89 (br, 1H),8.63 (br, 2H), 8.11 (t, J=1.5 Hz, 1H), 7.97 (dt, J=7.8, 1.5 Hz, 1H),7.62 (dt, J=7.8, 1.5 Hz, 1H), 7.46 (t, J=7.8 Hz, 1H), 7.41 (br, 2H),7.36 (d, J=2.6 Hz, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4, 2.6 Hz,1H), 6.26 (s, 1H), 3.89 (s, 3H), 2.85 (s, 2H), 1.37 (s, 6H).

EXAMPLE 93(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-(pyridin-4-yl)ethyl)phenyl)ethan-1-one

Under atmosphere of argon, to the compound prepared in example 92 (0.22g) were added 10% palladium carbon (0.02 g) and methanol (10 ml). Underatmosphere of hydrogen the mixture was stirred for 6 hours at roomtemperature. The reaction mixture was filtered over celite. The filtratewas concentrated. The residue was purified by column chromatography onsilica gel (ethyl acetate) to give the compound of the present inventionhaving the following physical data.

TLC: Rf0.56 (ethyl acetate); NMR (CDCl₃): δ 11.88 (br, 1H), 8.49 (dd,J=4.5, 1.8 Hz, 2H), 7.81-7.75 (m, 2H), 7.34 (d, J=2.7 Hz, 1H), 7.34 (t,J=7.7 Hz, 1H), 7.21 (m, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.10 (dd, J=4.5,1.8 Hz, 2H), 6.99 (dd, J=8.3, 2.7 Hz, 1H), 6.24 (s, 1H), 3.89 (s, 3H),3.05-2.92 (m, 4H), 2.84 (s, 2H), 1.36 (s, 6H).

EXAMPLE 94(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(2-hydroxypyridin-5-yl)ethan-1-one

To a solution of hexamethyldisilathiane (1 ml) in1,3-dimethyl-2-imidazolidinone (5 ml) was added sodium methoxide (0.24g) and the mixture was stirred for 1 hour at room temperature. To thereaction solution was added the compound prepared in example 86(14)(0.43 g) and the mixture was stirred for 1 hour at 150° C. The reactionmixture was allowed to cool to room temperature and thereto was addedwater and the mixture was extracted with ethyl acetate. The extract waswashed with water and brine, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (ethyl acetate:methanol=1:0→50:1→40:1) and thus purifiedcompound was sonicated to give the compound of the present invention(0.22 g) having the following physical data.

TLC: Rf0.64 (chloroform:methanol:water=10:2:0.1); NMR (CDCl₃): δ 12.44(br, 1H), 11.62 (br, 1H), 8.11-8.06 (m, 2H), 7.26 (d, J=2.7 Hz, 1H),7.13 (d, J=8.4 Hz, 1H), 7.00 (dd, J=8.4, 2.7 Hz, 1H), 6.63 (m, 1H), 5.98(s, 1H), 3.90 (s, 3H), 2.82 (s, 2H), 1.34 (s, 6H).

EXAMPLE 95(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)ethan-1-one

To a solution of the compound prepared in example 94 (0.72 g) intetrahydrofuran (1 ml) and dimethylformamide (1 ml) were added potassiumcarbonate (46 mg) and methyl iodide (21 μl) and the mixture was stirredfor 6 hours at room temperature. To the reaction mixture was added waterand the mixture was extracted with ethyl acetate. The extract was washedwith water and brine, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (ethyl acetate) to give the compound of the present invention(76 mg) having the following physical data.

TLC: Rf0.35 (ethyl acetate:methanol=40:1); NMR (CDCl₃): δ 11.67 (br,1H), 8.11 (d, J=2.8 Hz, 1H), 7.88 (dd, J=8.5, 2.8 Hz, 1H), 7.29 (d,J=2.5 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 7.00 (dd, J=8.2, 2.5 Hz, 1H),6.57 (d, J=8.5 Hz, 1H), 5.98 (s, 1H), 3.88 (s, 3H), 3.63 (s, 3H), 2.83(s, 2H), 1.34 (s, 6H).

EXAMPLE 96-EXAMPLE 96(2)

By the same procedure as described in reference example 11→referenceexample 6→example 11→example 42 using7-methoxy-4-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-one inplace of the compound prepared in reference example 10 and acorresponding derivative in place of benzoylmethyl bromide, thefollowing compounds of the present invention were given.

EXAMPLE 96(Z)-2-(4-hydroxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

TLC: Rf0.48 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.78 (br s, 1H),7.99 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H),7.31 (d, J=2.7 Hz, 1H), 7.09 (dd, J=8.4, 2.7 Hz, 1H), 6.24 (s, 1H), 4.48(d, J=7.5 Hz, 1H), 3.90 (s, 3H), 1.96 (d, J=7.5 Hz, 1H), 1.43 (s, 3H),1.28 (s, 3H).

EXAMPLE 96(1)(Z)-2-(4-hydroxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-methoxyphenyl)ethan-1-one

TLC: Rf0.31 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 1.22 (s, 3H) 1.43(s, 3H) 2.92 (d, J=8.06 Hz, 1H) 3.85 (s, 6H) 4.40 (d, J=8.06 Hz, 1H)6.17 (s, 1H) 6.87 (d, J=8.73 Hz, 2H) 7.02 (dd, J=8.39, 2.35 Hz, 1H) 7.18(d, J=2.35 Hz, 1H) 7.42 (d, J=8.39 Hz, 1H) 7.83 (d, J=8.73 Hz, 2H) 11.50(s, 1H).

EXAMPLE 96(2)(Z)-2-(4-hydroxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-nitrophenyl)ethan-1-one

TLC: Rf0.41 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 1.18 (s, 3H)1.24 (s, 3H) 3.87 (s, 3H) 4.44 (d, J=5.71 Hz, 1H) 5.74 (d, J=5.71 Hz,1H) 6.54 (s, 1H) 7.17 (dd, J=8.39, 2.52 Hz, 1H) 7.47 (d, J=8.39 Hz, 1H)7.59 (d, J=2.52 Hz, 1H) 8.26 (s, 4H) 11.95 (s, 1H).

EXAMPLE 97(Z)-2-(4-oxo-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-cyanophenyl)ethan-1-one

By the same procedure as described in example 43 using the compoundprepared in example 96 in place of the compound prepared in example 42,the compound of the present invention having the following physical datawas given.

TLC: Rf0.45 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 12.44 (br s, 1H),8.18 (d, J=8.7 Hz, 1H), 8.03 (d, J=8.4 Hz, 2H), 7.76 (d, J=8.4 Hz, 2H),7.44 (d, J=2.4 Hz, 1H), 7.21 (dd, J=8.7, 2.4 Hz, 1H), 6.45 (s, 1H), 3.99(s, 3H), 1.61 (s, 6H).

EXAMPLE 98(Z)-2-(4-hydroxy-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-aminophenyl)ethan-1-one

By the same procedure as described in example 58 using the compoundprepared in example 96(2) in place of the compound prepared in example56, the compound of the present invention having the following physicaldata was given.

TLC: Rf0.70 (ethyl acetate); NMR (DMSO-d₆): δ 1.07 (s, 3H) 1.21 (s, 3H)3.85 (s, 3H) 4.39 (d, J=5.88 Hz, 1H) 5.65 (m, 3H) 6.29 (s, 1H) 6.54 (d,J=8.73 Hz, 2H) 7.10 (dd, J=8.48, 2.27 Hz, 1H) 7.44 (m, 2H) 7.74 (d,J=8.73 Hz, 2H) 11.51 (s, 1H).

EXAMPLE 99-EXAMPLE 99(164)

The compounds of example 99 to example 99(164) were prepared accordingto the following method.

To a solution of a carboxylic acid (15 μmol) in pyridine (30 μl) wereadded a solution of amine 1 or amine 2 (30 μmol) inN,N-dimethylformamide (120 μl), a solution of HOAt (30 mmol,1-hydroxy-7-azabenzotriazole) in N,N-dimethylformamide (60 μl) andPS-Carbodiimide (ca. 45 mg, Argonaut Technologies Inc.) and the mixturewas allowed to stand overnight at room temperature. To the mixture wereadded PS-Isocyanate (ca. 60 mg, Argonaut Technologies Inc.) andPS-Trisamine (ca. 25 mg, Argonaut Technologies Inc.) and the resin wasfiltered and was washed with methylene chloride (3 ml). The filtrate wasconcentrated to give an amide compound. The condition under which HPLCwas measured is as follows.

-   Column: XTerra C18, 4.6×50 mm (5 um)-   Rate of flow: 3 ml/min, μ-   Solvent-   Solvent A: a 0.1% aqueous solution of trifluoroacetic acid,-   Solvent B: a 0.1% solution of trifluoroacetic acid in acetonitrile-   Ratio of solvent:

At first, the ratio of solvent A/solvent B was fixed to 95/5 for first0.5 minute. Next the ratio was changed to 0/100 linearly in 2.5 minutesand the ratio was fixed to 0/100 for 0.5 minute. Afterwards, the ratiowas changed to 95/5 in 0.01 minute and the ratio was fixed to 95/5 for1.49 minutes.

EXAMPLE 99(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclobutylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.97; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(1)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(cyclopentylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 419 (M+H)⁺.

EXAMPLE 99(2)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((cyclohexylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.27; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 99(3)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-(2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.52; Mass (ESI, Pos. 20V) m/z 409 (M+H)⁺.

EXAMPLE 99(4)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(1,3,4-thiadiazol-2-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.83; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(5)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-ethylpyrrolidin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.40; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(6)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((furan-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 431 (M+H)⁺.

EXAMPLE 99(7)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(1,3-thiazolidin-3-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 99(8) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin1-ylidene)-1-(3-(pyrrolidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(9)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((tetrahydrofuran-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.82; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(10)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-methylpiperazin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.27; Mass (ESI, Pos. 20V): m/z 434 (M+H)⁺.

EXAMPLE 99(11)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(morpholin-4-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.71; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(12)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(thiomorpholin-4-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(13)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(morpholin-4-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 464 (M+H)⁺.

EXAMPLE 99(14)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.35; Mass (ESI, Pos. 20V): m/z 442 (M+H)⁺.

EXAMPLE 99(15)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.34; Mass (ESI, Pos. 20V): m/z 456 (M+H)⁺.

EXAMPLE 99(16)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(pyridin-3-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.40; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(17)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-3-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 442 (M+H)⁺.

EXAMPLE 99(18)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(pyridin-4-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.43; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(19)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-ethoxycarbonylpiperidin-4-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 99(20)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(piperidin-1-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.40; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(21)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(phenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 99(22)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.20; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(23)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(24)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(t-butylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 99(25)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(benzylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 99(26)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-chlorobenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 99(27)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-methoxybenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 99(28)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,2-dimethylpropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(29)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methylpropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 99(30)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(phenylamino)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.61; Mass (ESI, Pos. 20V): m/z 470 (M+H)⁺.

EXAMPLE 99(31)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(acetylamino)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.51; Mass (ESI, Pos. 20V): m/z 436 (M+H)⁺.

EXAMPLE 99(32)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.73; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 99(33)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-phenylethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.09; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 99(34)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-phenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 99(35)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dilhydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N,N-dimethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.74; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 99(36)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-benzylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 99(37)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-phenethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 99(38)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((cyclopropylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.95; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(39)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(ethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.80; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 99(40)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(3-hydroxypiperidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.60; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(41)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(isopropylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 99(42)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(thiophen-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 99(43)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((5-methylfuran-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(44)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(((1S)-1-hydroxymethyl-3-methylthiopropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.74; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 99(45)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1,3-dioxaindan-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 99(46)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(4-(2-hydroxyethyl)piperazin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.25; Mass (ESI, Pos. 20V): m/z 464 (M+H)⁺.

EXAMPLE 99(47)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((quinolin-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.45; Mass (ESI, Pos. 20V): m/z 478 (M+H)⁺.

EXAMPLE 99(48)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((quinolin-6-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.50; Mass (ESI, Pos. 20V): m/z 478 (M+H)⁺.

EXAMPLE 99(49)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-cyanophenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 452 (M+H)⁺.

EXAMPLE 99(50)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-hydroxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.87; Mass (ESI, Pos. 20V): m/z 443 (M+H)⁺.

EXAMPLE 99(51)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-hydroxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 443 (M+H)⁺.

EXAMPLE 99(52)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-dimethylaminoethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.31; Mass (ESI, Pos. 20V): m/z 422 (M+H)⁺.

EXAMPLE 99(53)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-(2-hydroxyethoxy)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.51; Mass (ESI, Pos. 20V): m/z 439 (M+H)⁺.

EXAMPLE 99(54)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.51; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 99(55)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-propynylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.83; Mass (ESI, Pos. 20V): m/z 389 (M+H)⁺.

EXAMPLE 99(56)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2-propenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 99(57)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-methylbutyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(58)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-dimethylaminopropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 436 (M+H)⁺.

EXAMPLE 99(59)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-ethoxypropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(60)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-(3-(N-methyl-N-(2,2-dimethoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.84; Mass (ESI, Pos. 20V): m/z 453 (M+H)⁺.

EXAMPLE 99(61)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((N-methyl-N-hydroxycarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.61; Mass (ESI, Pos. 20V): m/z 381 (M+H)⁺.

EXAMPLE 99(62)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(bis(2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.84; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 99(63)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((3-chlorobenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.18; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 99(64)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-acetylpiperazin-1-yl)carbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.54; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(65)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.68; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(66)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(2,6-dimethylmorpholin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 99(67)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.33; Mass (ESI, Pos. 20V): m/z 470 (M+H)⁺.

EXAMPLE 99(68)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(((2,2,2-trifluoroethyl)amino)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 448 (M+H)⁺.

EXAMPLE 99(69)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1,1-diethyl-2-propynyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.17; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(70)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((pyridin-2-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.53; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(71)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((4-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.07; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(72)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1H-indazol-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 99(73)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((1-oxidopyridin-2-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 444 (M+H)⁺.

EXAMPLE 99(74)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((thiophen-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 99(75)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-ethylthioethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 439 (M+H)⁺.

EXAMPLE 99(76)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2,2,2-trifluoroethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.97; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 99(77)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-(furan-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(78)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-propyl-N-(2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.73; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(79)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(N-methyl-N-(2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.78; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 99(80)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-((2-mercaptoethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.37; Mass (ESI, Pos. 20V): m/z 411 (M+H)⁺.

EXAMPLE 99(81)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(3-(methylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.68; Mass (ESI, Pos. 20V): m/z 365 (M+H)⁺.

EXAMPLE 99(82)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclobutylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.95; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(83)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(cyclopentylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.02; Mass (ESI, Pos. 20V): m/z 419 (M+H)⁺.

EXAMPLE 99(84)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((cyclohexylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.25; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 99(85)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-(2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.51; Mass (ESI, Pos. 20V): m/z 409 (M+H)⁺.

EXAMPLE 99(86)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(1,3,4-thiadiazol-2-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.83; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(87)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-ethylpyrrolidin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.41; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(88)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((furan-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 431 (M+H)⁺.

EXAMPLE 99(89)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(1,3′-thiazolidin-3-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 99(90)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(pyrrolidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.86; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(91)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4,5-dihydro-1,3-thiazol-2-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.74; Mass (ESI, Pos. 20V): m/z 436 (M+H)⁺.

EXAMPLE 99(92)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((tetrahydrofuran-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.78; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(93)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-methylpiperazin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.26; Mass (ESI, Pos. 20V): m/z 434 (M+H)⁺.

EXAMPLE 99(94)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(morpholin-4-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.72; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(95)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(thiomorpholin-4-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.94; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(96)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(morpholin-4-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.33; Mass (ESI, Pos. 20V): m/z 464 (M+H)⁺.

EXAMPLE 99(97)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.34; Mass (ESI, Pos. 20V): m/z 442 (M+H)⁺.

EXAMPLE 99(98)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.34; Mass (ESI, Pos. 20V): m/z 456 (M+H)⁺.

EXAMPLE 99(99)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(pyridin-3-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.41; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(100)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-3-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 442 (M+H)⁺.

EXAMPLE 99(101)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(pyridin-4-ylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.44; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(102)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-ethoxycarbonylpiperidin-4-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.90; Mass (ESI, Pos. 20V): m/z 506 (M+H)⁺.

EXAMPLE 99(103)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(piperidin-1-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.39; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(104)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(phenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 427 (M+H)⁺.

EXAMPLE 99(105)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.22; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(106)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(107)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(t-butylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 99(108)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(benzylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 99(109)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-chlorobenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 99(110)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-methoxybenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.03; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 99(111)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,2-dimethylpropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(112)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methylpropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.98; Mass (ESI, Pos. 20V): m/z 407 (M+H)⁺.

EXAMPLE 99(113)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(phenylamino)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.59; Mass (ESI, Pos. 20V): m/z 470 (M+H)⁺.

EXAMPLE 99(114)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(acetylamino)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.49; Mass (ESI, Pos. 20V): m/z 436 (M+H)⁺.

EXAMPLE 99(115)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.72; Mass (ESI, Pos. 20V) m/z 409 (M+H)⁺.

EXAMPLE 99(116)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-phenylethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.08; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 99(117)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-phenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 441 (M+H)⁺.

EXAMPLE 99(118)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N,N-dimethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.73; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 99(119)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-benzylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.12; Mass (ESI, Pos. 20V): m/z 455 (M+H)⁺.

EXAMPLE 99(120)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-phenethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.13; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 99(121)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((cyclopropylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.93; Mass (ESI, Pos. 20V): m/z 405 (M+H)⁺.

EXAMPLE 99(122)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(ethylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.77; Mass (ESI, Pos. 20V): m/z 379 (M+H)⁺.

EXAMPLE 99(123)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(3-hydroxypiperidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.62; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(124)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(isopropylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.88; Mass (ESI, Pos. 20V): m/z 393 (M+H)⁺.

EXAMPLE 99(125)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(thiophen-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.04; Mass (ESI, Pos. 20V): m/z 461 (M+H)⁺.

EXAMPLE 99(126)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((5-methylfuran-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(127)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(((1S)-1-hydroxymethyl-3-methylthiopropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.72; Mass (ESI, Pos. 20V): m/z 469 (M+H)⁺.

EXAMPLE 99(128)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1,3-dioxaindan-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.05; Mass (ESI, Pos. 20V): m/z 471 (M+H)⁺.

EXAMPLE 99(129)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(4-(2-hydroxyethyl)piperazin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.24; Mass (ESI, Pos. 20V): m/z 464 (M+H)⁺.

EXAMPLE 99(130)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((quinolin-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.43; Mass (ESI, Pos. 20V): m/z 478 (M+H)⁺.

EXAMPLE 99(131)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((quinolin-6-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.52; Mass (ESI, Pos. 20V): m/z 478 (M+H)⁺.

EXAMPLE 99(132)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-cyanophenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.10; Mass (ESI, Pos. 20V): m/z 452 (M+H)⁺.

EXAMPLE 99(133)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-hydroxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.85; Mass (ESI, Pos. 20V): m/z 443 (M+H)⁺.

EXAMPLE 99(134)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-hydroxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.81; Mass (ESI, Pos. 20V): m/z 443 (M+H)⁺.

EXAMPLE 99(135)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-dimethylaminoethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.31; Mass (ESI, Pos. 20V): m/z 422 (M+H)⁺.

EXAMPLE 99(136)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-(2-hydroxyethoxy)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.50; Mass (ESI, Pos. 20V): m/z 439 (M+H)⁺.

EXAMPLE 99(137)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.50; Mass (ESI, Pos. 20V): m/z 395 (M+H)⁺.

EXAMPLE 99(138)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-propynylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.80; Mass (ESI, Pos. 20V): m/z 389 (M+H)⁺.

EXAMPLE 99(139)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2-propenylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.84; Mass (ESI, Pos. 20V): m/z 391 (M+H)⁺.

EXAMPLE 99(140)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-methylbutyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.11; Mass (ESI, Pos. 20V): m/z 421 (M+H)⁺.

EXAMPLE 99(141)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-dimethylaminopropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 436 (M+H)⁺.

EXAMPLE 99(142)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-ethoxypropyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.88; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(143)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-(2,2-dimethoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.83; Mass (ESI, Pos. 20V): m/z 453 (M+H)⁺.

EXAMPLE 99(144)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((N-methyl-N-hydroxycarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.73; Mass (ESI, Pos. 20V): m/z 381 (M+H)⁺.

EXAMPLE 99(145)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(bis(2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.84; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 99(146)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((3-chlorobenzyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 475 (M+H)⁺.

EXAMPLE 99(147)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-acetylpiperazin-1-yl)carbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.56; Mass (ESI, Pos. 20V): m/z 462 (M+H)⁺.

EXAMPLE 99(148)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.66; Mass (ESI, Pos. 20V): m/z 435 (M+H)⁺.

EXAMPLE 99(149)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(2,6-dimethylmorpholin-1-ylcarbonyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.91; Mass (ESI, Pos. 20V): m/z 449 (M+H)⁺.

EXAMPLE 99(150)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.32; Mass (ESI, Pos. 20V): m/z 470 (M+H)⁺.

EXAMPLE 99(151)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(((2,2,2-trifluoroethyl)amino)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.89; Mass (ESI, Pos. 20V): m/z 448 (M+H)⁺.

EXAMPLE 99(152)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1,1-diethyl-2-propynyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.16; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(153)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((pyridin-2-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.51; Mass (ESI, Pos. 20V): m/z 428 (M+H)⁺.

EXAMPLE 99(154)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((4-methoxyphenyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.06; Mass (ESI, Pos. 20V): m/z 457 (M+H)⁺.

EXAMPLE 99(155)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1Hindazol-5-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.72; Mass (ESI, Pos. 20V): m/z 467 (M+H)⁺.

EXAMPLE 99(156)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((1-oxidopyridin-2-yl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.85; Mass (ESI, Pos. 20V): m/z 444 (M+H)⁺.

EXAMPLE 99(157)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((thiophen-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.01; Mass (ESI, Pos. 20V): m/z 447 (M+H)⁺.

EXAMPLE 99(158)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-ethylthioethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.00; Mass (ESI, Pos. 20V): m/z 439 (M+H)⁺.

EXAMPLE 99(159)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.95; Mass (ESI, Pos. 20V): m/z 433 (M+H)⁺.

EXAMPLE 99(160)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-(furan-2-ylmethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.99; Mass (ESI, Pos. 20V): m/z 445 (M+H)⁺.

EXAMPLE 99(161)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-propyl-N-(2-hydroxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.73; Mass (ESI, Pos. 20V): m/z 437 (M+H)⁺.

EXAMPLE 99(162)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(N-methyl-N-(2-methoxyethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.78; Mass (ESI, Pos. 20V): m/z 423 (M+H)⁺.

EXAMPLE 99(163)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-((2-mercaptoethyl)carbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 4.34; Mass (ESI, Pos. 20V): m/z 411 (M+H)⁺.

EXAMPLE 99(164)(Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(4-(methylcarbamoyl)phenyl)ethan-1-one

HPLC retention time (min.): 3.66; Mass (ESI, Pos. 20V): m/z 365 (M+H)⁺.

FORMULATION EXAMPLES FORMULATION EXAMPLE 1

The following components were admixed in a conventional method andpunched out to obtain 100 tablets each containing 50 mg of the activeingredient.

(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)- 5.0 gisoquinolin-1-ylidene)-1-cyclohexylethan-1-one Carboxymethyl cellulosecalcium (disintegrating agent) 0.2 g Magnesium stearate (lubricant) 0.1g Microcrystalline cellulose 4.7 g

FORMULATION EXAMPLE 2

The following components were admixed in a conventional method, and thesolution was sterilized in a conventional method, placed at 5 ml intoampoules and freeze-dried in a conventional method to thereby obtain 100ampoules each containing 20 mg of the active ingredient.

(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1- 2.0 gylidene)-1-cyclohexylethan-1-one Mannitol 20 g Distilled water 1000 ml

1. A compound of formula (I)

wherein R¹ and R² are each independently C1-8 alkyl; Z is —CR³R⁴—; R³and R⁴ are each independently, (1) hydrogen atom, (2) C1-8 alkyl, (3)C1-8 alkoxy, or (4) hydroxy; R⁵ and R⁶ are each independently, (1)hydrogen atom, or (2) C1-8 alkyl, or R⁵ and R⁶ may be taken togetherwith the carbon atom to which they are attached to form Cyc1; Cyc1,which is represented by R¹ and R², R³ and R⁴, R⁵ and R⁶ is, eachindependently, (1) C3-10 cycloalkyl, or (2) 3-10 membered monocyclicheteroring comprising 1-2 of heteroatom selected from oxygen, nitrogenand sulfur, and Cyc1 may be substituted with R¹⁰; R¹⁰ is (1) C1-8 alkyl,(2) C1-8 alkoxy, (3) hydroxy, (4) —COOR¹¹, (5) oxo, (6) —SO₂R¹², or (7)—COR¹³; R¹¹ is hydrogen atom, or C1-8 alkyl; R¹² and R¹³ are (1) C1-8alkyl, or (2) phenyl which may be substituted with C1-8 alkyl; R⁷ and R⁸are each independently, (1) hydrogen atom, (2) C1-8 alkyl, (3) C1-8alkoxy, (4) hydroxy, (5) cyano, (6) halogen atom, (7) —COOR¹⁴, (8)—CONR¹⁵R¹⁶, (9) Cyc2, (10) C2-8 alkenyl, (11) C2-8 alkynyl, (12)—NR⁵¹R⁵², (13) nitro, (14) formyl, (15) C2-8 acyl, (16) C1-8 alkylsubstituted with hydroxy, C1-8 alkoxy, Cyc2, —NR⁵¹R⁵², or —NR⁵³-Cyc2,(17) —NR⁵⁴COR⁵⁵, (18) —NR⁵⁶SO₂R⁵⁷, (19) —SO₂NR⁵⁸R⁵⁹, (20) C2-8 alkenylsubstituted with —COOR¹⁴, (21) —CH═N—OH, (22) —(C1-8alkylene)-NR⁶⁰—(C1-8 alkylene)-R⁶¹, (23) C1-8 alkylthio, (24) C1-8 alkylsubstituted with 1-3 of halogen atom, (25) C1-8 alkoxy substituted with1-3 of halogen atom, (26) C1-8 alkoxy substituted with Cyc2, (27)—O-Cyc2, (28) —OSO₂R⁶⁵, or (29) —CH═N—OR¹³⁷; R¹⁴ is hydrogen atom, orC1-8 alkyl; R¹⁵ and R¹⁶ are each independently hydrogen atom or C1-8alkyl; R⁵¹ and R⁵², R⁵⁸ and R⁵⁹ are each independently, hydrogen atom,or C1-8 alkyl; R⁵³, R⁵⁴, R⁵⁶ and R⁶⁰ are each independently, hydrogenatom, or C1-8 alkyl; R⁵⁵ is hydrogen atom, C1-8 alkyl, or C1-8 alkoxy;R⁵⁷ is C1-8 alkyl; R⁶¹ is —NR⁶²R⁶³ or hydroxy; R⁶² and R⁶³ are eachindependently, hydrogen atom, or C1-8 alkyl; R⁶⁵ is C1-8 alkyl; R¹³⁷ isC1-8 alkyl;

(hereinafter it is abbreviated as ring;) is Cyc2 wherein the group whichattaches to carbonyl is carbon; R⁷ R⁸ represented by ring are eachindependently (1) C3-15 mono-, bi- or tri-cyclic (fused or spiro)carboring, or (2) 3-15 membered mono-, bi- or tri-cyclic (fused orspiro) heteroring comprising 1-4 of heteroatoms selected from oxygen,nitrogen, and sulfur, and Cyc2 represented by ring is C3-15 mono-, bi-or tri-cyclic (fused or spiro) carboring selected from the groupconsisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane,cycloheptane, cyclooctane, cyclononane, cyclodecane, cycloundecane,cyclododecane, cyclotridodecane, bicyclo[3.3.0]octane,bicyclo[4.3.0]nonane, bicyclo[4.4.0]decane, spiro[4.4]nonane,spiro[4.5]decane, spiro[5.5]undecane, bicyclo[3.1.1]heptane, adamantan,noradamantan, and bicyclo[2.2.2]octane; Cyc2 may be substituted with 1-5of R¹⁷ or R¹⁷; R¹⁷ is (1) C1-8 alkyl, (2) C2-8 alkenyl, (3) C2-8alkynyl, (4) C1-8 alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7) halogenatom, (8) nitro, (9) oxo, (10) carboxy, (11) formyl, (12) cyano, (13)—NR¹⁸R¹⁹, (14) phenyl, phenoxy or phenylthio, which may be substitutedwith 1-5 of R²⁰, (15) C1-8 alkyl, C2-8 alkenyl, C1-8 alkoxy or C1-8alkylthio, which may be substituted with 1-5 of R²¹ (16) —OCOR²², (17)—CONR²³R²⁴, (18) —SO₂NR²⁵R²⁶ (19) —COOR²⁷, (20) —COCOOR²⁸, (21) —COR²⁹,(22) —COCOR³⁰, (23) —NR³¹COR³², (24) —SO₂R³³, (25) —NR³⁴SO₂R³⁵, or (26)—SOR⁶⁴; R¹⁸ and R¹⁹, R³¹ and R³⁴ are each independently, hydrogen atom,or C1-8 alkyl; R²⁰ and R²¹ are C1-8 alkyl, C1-8 alkoxy, hydroxy, halogenatom, nitro, or —COOR³⁶; R²² and R⁶⁴ are each independently C1-8 alkyl;R²³, R²⁴, R²⁵ and R²⁶ are each independently hydrogen atom, C1-8 alkyl,or phenyl; R²⁷, R²⁸, R²⁹, R³⁰, R³², R³³ and R³⁵ are (1) C1-8 alkyl, (2)C2-8 alkenyl, (3) C1-8 alkyl substituted with 1-5 of R³⁷, (4)diphenylmethyl, (5) triphenylmethyl, (6) Cyc3, (7) C1-8 alkyl or C2-8alkenyl substituted with Cyc3, (8) C1-8 alkyl substituted with —O-Cyc3,—S-Cyc3 or —SO₂-Cyc3; R³⁶ is hydrogen atom, or C1-8 alkyl; R³⁷ is C1-8alkoxy, C1-8 alkylthio, benzyloxy, halogen atom, nitro or —COOR³⁸; R³⁸is hydrogen atom, C1-8 alkyl or C2-8 alkenyl; Cyc3 is (1) C3-15 mono-,bi- or tri-cyclic (fused or spiro)carboring, or (2) 3-15 membered mono-,bi- or tri-cyclic (fused or spiro)heteroring comprising 1-4 ofheteroatom selected from oxygen, nitrogen and sulfur; Cyc3 may besubstituted with 1-5 of R³⁹; R³⁹ is (1) C1-8 alkyl, (2) C2-8 alkenyl,(3) C2-8 alkynyl, (4) C1-8 alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7)halogen atom,(8) nitro, (9) oxo, (10) cyano, (11) benzyl, (12)benzyloxy, (13) C1-8 alkyl, C1-8 alkoxy or C1-8 alkylthio substitutedwith 1-5 of R⁴⁰, (14) phenyl, phenoxy, phenylthio, phenylsulfonyl orbenzoyl which may be substituted with 1-5 of R⁴¹, (15) —OCOR⁴², (16)—SO₂R⁴³, (17) —NR⁴⁴COR⁴⁵, (18) —SO₂NR⁴⁶R⁴⁷, (19) —COOR⁴⁸, or (20)—NR⁴⁹R⁵⁰; R⁴⁰ is halogen atom; R⁴¹ is C1-8 alkyl, C1-8 alkoxy, halogenatom, or nitro; R⁴², R⁴³ and R⁴⁵ are C1-8 alkyl; R⁴⁴ and R⁴⁸ arehydrogen atom or C1-8 alkyl; R⁴⁶ and R⁴⁷, R⁴⁹ and R⁵⁰ are eachindependently, hydrogen atom or C1-8 alkyl; R^(17′) is (1) SH, (2)—NR⁶⁶CHO, (3) Cyc5, (4) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynylsubstituted with Cyc5, (5) —CO—(NH-amino acid residue-CO)_(n)—OH, (6)—NR⁶⁷CONR⁶⁸R⁶⁹, (7) —CONR⁷⁰NR⁷¹R⁷²,(8) —CONR⁷³OR⁷⁴,(9) —CONR⁷⁵COR⁷⁶,(10)—C(S)NR⁷⁷R⁷⁸,(11) —CONR⁷⁹C(S)COOR⁸⁰, (12) —NR⁸¹COCOOR⁸², (13)—NR⁸³COOR⁸⁴, (14) —CONR⁸⁵C(S)R⁸⁶, (15) —OCOR⁸⁷, (16) —SOR⁸⁸, (17)—CONR⁸⁹R⁹⁰, (18) —SO₂NR⁹¹R⁹², (19) —COOR⁹³, (20) —COCOOR⁹⁴, (21) —COR⁹⁵,(22) —COCOR⁹⁶, (23) —NR⁹⁷COR⁹⁸, (24) —SO₂R⁹⁹, (25) —NR¹⁰⁰SO₂R¹⁰¹, or(26) —NR¹⁰²R¹⁰³; n is an integer of 1 or 2; R⁶⁶, R⁷³, R⁷⁵, R⁷⁷, R⁷⁹,R⁸¹, R⁸³, R⁸⁵, R⁹⁷, R¹⁰⁰, and R¹⁰² are hydrogen atom, or C1-8 alkyl; R⁶⁷and R⁶⁸, R⁷⁰ and R⁷¹ are each independently, hydrogen atom, or C1-8alkyl; R⁸⁹ and R⁹¹ are (1) hydrogen atom,(2) C1-8 alkyl, (3) phenyl, or(4) C1-8 alkyl substituted with cyano or C1-8 alkoxy; R¹⁰³ is Cyc6; R⁶⁹,R⁷², R⁷⁴, R⁷⁶, R⁷⁸, R⁸⁰, R⁸², R⁸⁴, R⁸⁶, R⁸⁷, R⁸⁸, R⁹⁰ and R⁹² are (1)hydrogen atom, (2) C1-8 alkyl, (3) C2-8 alkenyl, (4) C2-8 alkynyl, (5)C1-8 alkyl substituted with 1-5 of R¹⁰⁴, (6) diphenylmethyl, (7)triphenylmethyl, (8) Cyc6, (9) C1-8 alkyl or C2-8 alkenyl substitutedwith Cyc6, or (10) C1-8 alkyl substituted with —O-Cyc6, —S-Cyc6 or—S02-Cyc6; R¹⁰⁴ is (1) C1-8 alkoxy, (2) C1-8 alkylthio, (3) benzyloxy,(4) halogen atom, (5) nitro, (6) —COOR¹⁰⁵, (7) cyano, (8) —NR¹⁰⁶R¹⁰⁷,(9) —NR¹⁰⁸COR¹⁰⁹, (10) hydroxy, (11) SH, (12) —SO₃H, (13) —S(O)OH, (14)—OSO₃H, (15) C2-8 alkenyloxy, (16) C2-8 alkynyloxy, (17) —COR¹¹⁰, (18)—SO₂R¹¹¹, or (19) C1-8 alkoxy or C1-8 alkylthio substituted withhydroxy; R¹⁰⁵ is hydrogen atom, C1-8 alkyl, or C2-8 alkenyl; R¹⁰⁶ andR¹⁰⁷ are each independently, hydrogen atom, or C1-8 alkyl; R¹⁰⁸ ishydrogen atom, or C1-8 alkyl; R¹⁰⁹ and R¹¹¹ are C1-8 alkyl; R¹¹⁰ is C1-8alkyl, or halogen atom; wherein R⁸², R⁸⁴ and R⁸⁶ are not hydrogen atom;wherein R⁸⁷ and R⁸⁸ are not hydrogen atom and C1-8 alkyl; wherein R⁹⁰and R⁹² are not hydrogen atom, C1-8 alkyl or phenyl; R⁹³, R⁹⁴, R⁹⁵, R⁹⁶,R⁹⁸, R⁹⁹ and R¹⁰¹ are (1) C2-8 alkynyl, (2) C1-8 alkyl substituted withR¹²⁸ which may be substituted with 1-4 of R¹²⁹, (3) Cyc8, (4) C1-8 alkylor C2-8 alkenyl substituted with Cyc8, or (5) C1-8 alkyl substitutedwith —O-Cyc8, —S-Cyc8 or —SO₂-Cyc8; R¹²⁸ is (1) cyano, (2) —NR¹⁰⁶R¹⁰⁷,(3) —NR¹⁰⁸COR¹⁰⁹, (4) hydroxy, (5) SH, (6) —SO₃H, (7) —S(O)OH, (8)—OSO₃H, (9) C2-8 alkenyloxy, (10) C2-8 alkynyloxy, (11) —COR¹¹⁰, (12)—SO₂R¹¹¹, or (13) C1-8 alkoxy or C1-8 alkylthio substituted withhydroxy; R¹²⁹ has the same meaning as R¹⁰⁴; Cyc5 and Cyc6 may besubstituted with 1-5 of R¹¹²; R¹¹² is (1) C1-8 alkyl, (2) C2-8 alkenyl,(3) C2-8 alkynyl, (4) C1-8 alkoxy, (5) C1-8 alkylthio, (6) hydroxy, (7)halogen atom, (8) nitro, (9) oxo, (10) cyano, (11) benzyl, (12)benzyloxy, (13) C1-8 alkyl, C1-8 alkoxy or C1-8 alkylthio substitutedwith 1-5 of R¹¹³, (14) phenyl, phenoxy, phenylthio or benzoyl, which maybe substituted with 1-5 of R¹¹⁴, (15) —COR¹¹⁵, (16) —SO₂R¹¹⁶, (17)—NR¹¹⁷COR¹¹⁸, (18) —SO₂NR¹¹⁹R¹²⁰, (19) —COOR¹²¹, (20) —NR¹²²R¹²³, (21)—COR¹²⁴, (22) —CONR¹²⁵R¹²⁶, (23) SH, (24) C1-8 alkyl substituted withhydroxy or —NR¹²⁷-benzoyl, or (25) Cyc7; R¹¹³ is halogen atom; R¹¹⁴ isC1-8 alkyl, C1-8 alkoxy, halogen atom, or nitro; R¹¹⁵, R¹¹⁶ and R¹¹⁸ areC1-8 alkyl; R¹¹⁷, R¹²¹, R¹²⁴ and R¹²⁷ are hydrogen atom, or C1-8 alkyl;R¹¹⁹ and R¹²⁰, R¹²² and R¹²³, R¹²⁵ and R¹²⁶ are each independently,hydrogen atom or C1-8 alkyl; Cyc7 may be substituted with 1-5 groupselected from (1) C1-8 alkyl, (2) C1-8 alkoxy, (3) halogen atom, or (4)nitro; Cyc8 may be substituted with R¹³⁰, and it further may besubstituted with 1-4 of R¹³¹; R¹³⁰ is (1) —COR¹²⁴, (2) —CONR¹²⁵R¹²⁶, (3)SH, (4) C1-8 alkyl substituted with hydroxy or —NR¹²⁷-benzoyl, or (5)Cyc7; R¹³¹ has the same meaning as R¹¹²; Cyc5, Cyc6, Cyc7 and Cyc8 are(1) C3-15 mono-, bi- or tri-cyclic (fused or spiro)carboring, or (2)3-15 membered mono-, bi- or tri-cyclic (fused or spiro)heteroringcomprising 1-4 of heteroatom selected from 1-4 of oxygen, nitrogen orsulfur; wherein when R^(17′) is Cyc5, Cyc5 is not phenyl which may besubstituted with 1-5 selected from C1-8 alkyl, C1-8 alkoxy, hydroxy,halogen atom, nitro, —COOH, or —COO—(C1-8 alkyl); wherein Cyc7 is notphenyl; Cyc4 is benzo;

(abbreviated as dashed line a hereafter;) and

(abbreviated as dashed line b hereafter;) are (1) a bond, or (2) adouble bond; R⁹ (1) does not exist or (2) is hydrogen atom; wherein 1)when dashed line a is a bond, dashed line b is a double bond, and R⁹does not exist, 2) when dashed line a is a double bond, dashed line b isa bond, and R⁹ is hydrogen atom and R⁶ does not exist, and 3)2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-phenylethan-1-oneis excluded, or a pharmacologically acceptable salt thereof.
 2. Thecompound according to claim 1, in formula (I), wherein (i) Z is —CR³R⁴—and at least either of R⁷ or R⁸ is (24) C1-8 alkyl substituted with 1-3of halogen atom, (25) C1-8 alkoxy substituted with 1-3 of halogen atom,(26) C1-8 alkoxy substituted with Cyc2, (27) —O-Cyc2, (28) —OSO₂R⁶⁵, or(29) —CH═N—OR¹³⁷, or (ii) Z is —CR³R⁴— and at least one Cyc2 which isrepresented by R⁷, R⁸ or ring is substituted with at least one R^(17′)or a pharmacologically acceptable salt thereof.
 3. The compoundaccording to claim 1, which is represented by formula (I′)

wherein, R¹ and R² are each independently, C1-8 alkyl, Z′ is —CR³′R⁴′—,R^(3′) and R⁴′ are each independently, hydrogen atom, C1-8 alkyl, orhydroxy, R^(7′) and R^(8′) are each independently, hydrogen atom, C1-8alkyl, C1-8 alkoxy, hydroxy, cyano, halogen atom, —COOR¹⁴, —CONR¹⁵R¹⁶,Cyc2, —NR⁵¹R⁵², formyl, hydroxy or C1-8 alkyl substituted with C1-8alkoxy, or —SO₂NR⁵⁸R⁵⁹, Cyc2 represented by

may be substituted with 1-5 of R^(17″), R^(17″) is C1-8 alkyl, C1-8alkoxy, hydroxy, halogen atom, nitro, oxo, (10) carboxy, (11) formyl,(12) cyano, (13) —NR¹⁸R¹⁹, (15) C1-8 alkyl substituted with 1-5 of R²¹,(17) —CONR²³R²⁴, (19) —COOR²⁷, (21) —COR²⁹, (23) —NR³¹COR³², or (25)—NR³⁴SO₂R³⁵ and the other symbols have the same meaning as claim 1, or apharmacologically acceptable salt thereof.
 4. The compound according toclaim 2, which is(Z)-2-(7-bromomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,or a pharmacologically acceptable salt thereof.
 5. The compoundaccording to claim 3, which is (1)(Z)-2-(7-t-butylsulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,(2)(Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one,(3)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one,(4)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one,(5)(Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,(6)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,(7)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cyclohexylethan-1-one,(8)(Z)-2-(7-hydroxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one,(9)(Z)-2-(7-(1-hydroxy-1-methylethyl)-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one,(10)(Z)-2-(7-(1-hydroxyethyl)-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-cycloheptylethan-1-one,(11)(Z)-2-(7-methoxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,or (12)(Z)-2-(7-sulfamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinolin-1-ylidene)-1-(adamantan-1-yl)ethan-1-one,or a pharmacologically acceptable salt thereof. or a pharmacologicallyacceptable salt thereof.
 6. A pharmaceutical composition comprising thecompound according to claim 1 or a pharmacologically acceptable saltthereof as active ingredient and a pharmaceutically acceptable carrier.7. A pharmaceutical composition comprising the compound according toclaim 2, or a pharmacologically acceptable salt as active ingredient anda pharmaceutically acceptable carrier.
 8. A method for treating allergicdiseases, rejection of an organ transplant, graft versus host disease(GVHD), osteoporosis, bone fracture, re-stenosis, arteriosclerosis,obesity, ischemic reperfusion injury, or depression, which comprisesadministering the compound according to claim 1 or a pharmacologicallyacceptable salt thereof.
 9. A method for treating asthma, allergyrhinitis, atopic dermatitis, rheumatism, postoperative pain and/orcarcinomatous pain, which comprises administering the compound accordingto claim 2, or a pharmacologically acceptable salt as active ingredient.